Author: "Kinhult Ståhlbom, A" / Publication Year Range: Last 50 years - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Kinhult Ståhlbom, A"' showing total 35 results

Start Over Author "Kinhult Ståhlbom, A" Publication Year Range Last 50 years

35 results on '"Kinhult Ståhlbom, A"'

1. Extended genetic analysis and tumor characteristics in over 4600 women with suspected hereditary breast and ovarian cancer

Author: Anna Öfverholm, Therese Törngren, Anna Rosén, Brita Arver, Zakaria Einbeigi, Karin Haraldsson, Anne Kinhult Ståhlbom, Ekaterina Kuchinskaya, Annika Lindblom, Beatrice Melin, Ylva Paulsson-Karlsson, Marie Stenmark-Askmalm, Emma Tham, Anna von Wachenfeldt, Anders Kvist, Åke Borg, and Hans Ehrencrona
Subjects: BRCA1, BRCA2, Genetic testing, Cancer, Breast cancer, Ovarian cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Genetic screening for pathogenic variants (PVs) in cancer predisposition genes can affect treatment strategies, risk prediction and preventive measures for patients and families. For decades, hereditary breast and ovarian cancer (HBOC) has been attributed to PVs in the genes BRCA1 and BRCA2, and more recently other rare alleles have been firmly established as associated with a high or moderate increased risk of developing breast and/or ovarian cancer. Here, we assess the genetic variation and tumor characteristics in a large cohort of women with suspected HBOC in a clinical oncogenetic setting. Methods Women with suspected HBOC referred from all oncogenetic clinics in Sweden over a six-year inclusion period were screened for PVs in 13 clinically relevant genes. The genetic outcome was compared with tumor characteristics and other clinical data collected from national cancer registries and hospital records. Results In 4622 women with breast and/or ovarian cancer the overall diagnostic yield (the proportion of women carrying at least one PV) was 16.6%. BRCA1/2 PVs were found in 8.9% of women (BRCA1 5.95% and BRCA2 2.94%) and PVs in the other breast and ovarian cancer predisposition genes in 8.2%: ATM (1.58%), BARD1 (0.45%), BRIP1 (0.43%), CDH1 (0.11%), CHEK2 (3.46%), PALB2 (0.84%), PTEN (0.02%), RAD51C (0.54%), RAD51D (0.15%), STK11 (0) and TP53 (0.56%). Thus, inclusion of the 11 genes in addition to BRCA1/2 increased diagnostic yield by 7.7%. The yield was, as expected, significantly higher in certain subgroups such as younger patients, medullary breast cancer, higher Nottingham Histologic Grade, ER-negative breast cancer, triple-negative breast cancer and high grade serous ovarian cancer. Age and tumor subtype distributions differed substantially depending on genetic finding. Conclusions This study contributes to understanding the clinical and genetic landscape of breast and ovarian cancer susceptibility. Extending clinical genetic screening from BRCA1 and BRCA2 to 13 established cancer predisposition genes almost doubles the diagnostic yield, which has implications for genetic counseling and clinical guidelines. The very low yield in the syndrome genes CDH1, PTEN and STK11 questions the usefulness of including these genes on routine gene panels.
Published: 2023
Full Text: View/download PDF

2. Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author: de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E., Pedersen, Nancy L., Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M., Bis, Joshua C., Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C., Lemstra, Afina W., Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A. L., Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anaïs, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L., Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M., Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G., Kunkle, Brian W., Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B., Chillotti, Caterina, Reynolds, Chandra A., Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L., Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K., Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L., Vogelgsang, Jonathan, Pineda, Juan A., Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A., Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M. Arfan, Deniz-Naranjo, M. Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A., Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M., Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J., Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H., Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T., Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M., Seidu, Nazib M., Banaj, Nerisa, Armstrong, Nicola J., Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Mecocci, Patrizia, Hoffmann, Per, Holmans, Peter A., Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N., Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A. L., Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J., Álvarez, Victoria, Lleó, Alberto, Real, Luis M., Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D., Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M., Mather, Karen A., Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A., Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M., Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J., and Ruiz, Agustín
Published: 2023
Full Text: View/download PDF

3. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author: Itziar de Rojas, Sonia Moreno-Grau, Niccolo Tesi, Benjamin Grenier-Boley, Victor Andrade, Iris E. Jansen, Nancy L. Pedersen, Najada Stringa, Anna Zettergren, Isabel Hernández, Laura Montrreal, Carmen Antúnez, Anna Antonell, Rick M. Tankard, Joshua C. Bis, Rebecca Sims, Céline Bellenguez, Inés Quintela, Antonio González-Perez, Miguel Calero, Emilio Franco-Macías, Juan Macías, Rafael Blesa, Laura Cervera-Carles, Manuel Menéndez-González, Ana Frank-García, Jose Luís Royo, Fermin Moreno, Raquel Huerto Vilas, Miquel Baquero, Mónica Diez-Fairen, Carmen Lage, Sebastián García-Madrona, Pablo García-González, Emilio Alarcón-Martín, Sergi Valero, Oscar Sotolongo-Grau, Abbe Ullgren, Adam C. Naj, Afina W. Lemstra, Alba Benaque, Alba Pérez-Cordón, Alberto Benussi, Alberto Rábano, Alessandro Padovani, Alessio Squassina, Alexandre de Mendonça, Alfonso Arias Pastor, Almar A. L. Kok, Alun Meggy, Ana Belén Pastor, Ana Espinosa, Anaïs Corma-Gómez, Angel Martín Montes, Ángela Sanabria, Anita L. DeStefano, Anja Schneider, Annakaisa Haapasalo, Anne Kinhult Ståhlbom, Anne Tybjærg-Hansen, Annette M. Hartmann, Annika Spottke, Arturo Corbatón-Anchuelo, Arvid Rongve, Barbara Borroni, Beatrice Arosio, Benedetta Nacmias, Børge G. Nordestgaard, Brian W. Kunkle, Camille Charbonnier, Carla Abdelnour, Carlo Masullo, Carmen Martínez Rodríguez, Carmen Muñoz-Fernandez, Carole Dufouil, Caroline Graff, Catarina B. Ferreira, Caterina Chillotti, Chandra A. Reynolds, Chiara Fenoglio, Christine Van Broeckhoven, Christopher Clark, Claudia Pisanu, Claudia L. Satizabal, Clive Holmes, Dolores Buiza-Rueda, Dag Aarsland, Dan Rujescu, Daniel Alcolea, Daniela Galimberti, David Wallon, Davide Seripa, Edna Grünblatt, Efthimios Dardiotis, Emrah Düzel, Elio Scarpini, Elisa Conti, Elisa Rubino, Ellen Gelpi, Eloy Rodriguez-Rodriguez, Emmanuelle Duron, Eric Boerwinkle, Evelyn Ferri, Fabrizio Tagliavini, Fahri Küçükali, Florence Pasquier, Florentino Sanchez-Garcia, Francesca Mangialasche, Frank Jessen, Gaël Nicolas, Geir Selbæk, Gemma Ortega, Geneviève Chêne, Georgios Hadjigeorgiou, Giacomina Rossi, Gianfranco Spalletta, Giorgio Giaccone, Giulia Grande, Giuliano Binetti, Goran Papenberg, Harald Hampel, Henri Bailly, Henrik Zetterberg, Hilkka Soininen, Ida K. Karlsson, Ignacio Alvarez, Ildebrando Appollonio, Ina Giegling, Ingmar Skoog, Ingvild Saltvedt, Innocenzo Rainero, Irene Rosas Allende, Jakub Hort, Janine Diehl-Schmid, Jasper Van Dongen, Jean-Sebastien Vidal, Jenni Lehtisalo, Jens Wiltfang, Jesper Qvist Thomassen, Johannes Kornhuber, Jonathan L. Haines, Jonathan Vogelgsang, Juan A. Pineda, Juan Fortea, Julius Popp, Jürgen Deckert, Katharina Buerger, Kevin Morgan, Klaus Fließbach, Kristel Sleegers, Laura Molina-Porcel, Lena Kilander, Leonie Weinhold, Lindsay A. Farrer, Li-San Wang, Luca Kleineidam, Lucia Farotti, Lucilla Parnetti, Lucio Tremolizzo, Lucrezia Hausner, Luisa Benussi, Lutz Froelich, M. Arfan Ikram, M. Candida Deniz-Naranjo, Magda Tsolaki, Maitée Rosende-Roca, Malin Löwenmark, Marc Hulsman, Marco Spallazzi, Margaret A. Pericak-Vance, Margaret Esiri, María Bernal Sánchez-Arjona, Maria Carolina Dalmasso, María Teresa Martínez-Larrad, Marina Arcaro, Markus M. Nöthen, Marta Fernández-Fuertes, Martin Dichgans, Martin Ingelsson, Martin J. Herrmann, Martin Scherer, Martin Vyhnalek, Mary H. Kosmidis, Mary Yannakoulia, Matthias Schmid, Michael Ewers, Michael T. Heneka, Michael Wagner, Michela Scamosci, Miia Kivipelto, Mikko Hiltunen, Miren Zulaica, Montserrat Alegret, Myriam Fornage, Natalia Roberto, Natasja M. van Schoor, Nazib M. Seidu, Nerisa Banaj, Nicola J. Armstrong, Nikolaos Scarmeas, Norbert Scherbaum, Oliver Goldhardt, Oliver Hanon, Oliver Peters, Olivia Anna Skrobot, Olivier Quenez, Ondrej Lerch, Paola Bossù, Paolo Caffarra, Paolo Dionigi Rossi, Paraskevi Sakka, Per Hoffmann, Peter A. Holmans, Peter Fischer, Peter Riederer, Qiong Yang, Rachel Marshall, Rajesh N. Kalaria, Richard Mayeux, Rik Vandenberghe, Roberta Cecchetti, Roberta Ghidoni, Ruth Frikke-Schmidt, Sandro Sorbi, Sara Hägg, Sebastiaan Engelborghs, Seppo Helisalmi, Sigrid Botne Sando, Silke Kern, Silvana Archetti, Silvia Boschi, Silvia Fostinelli, Silvia Gil, Silvia Mendoza, Simon Mead, Simona Ciccone, Srdjan Djurovic, Stefanie Heilmann-Heimbach, Steffi Riedel-Heller, Teemu Kuulasmaa, Teodoro del Ser, Thibaud Lebouvier, Thomas Polak, Tiia Ngandu, Timo Grimmer, Valentina Bessi, Valentina Escott-Price, Vilmantas Giedraitis, Vincent Deramecourt, Wolfgang Maier, Xueqiu Jian, Yolande A. L. Pijnenburg, EADB contributors, DEGESCO consortium, IGAP (ADGC, CHARGE, EADI, GERAD), PGC-ALZ consortia, Patrick Gavin Kehoe, Guillermo Garcia-Ribas, Pascual Sánchez-Juan, Pau Pastor, Jordi Pérez-Tur, Gerard Piñol-Ripoll, Adolfo Lopez de Munain, Jose María García-Alberca, María J. Bullido, Victoria Álvarez, Alberto Lleó, Luis M. Real, Pablo Mir, Miguel Medina, Philip Scheltens, Henne Holstege, Marta Marquié, María Eugenia Sáez, Ángel Carracedo, Philippe Amouyel, Gerard D. Schellenberg, Julie Williams, Sudha Seshadri, Cornelia M. van Duijn, Karen A. Mather, Raquel Sánchez-Valle, Manuel Serrano-Ríos, Adelina Orellana, Lluís Tárraga, Kaj Blennow, Martijn Huisman, Ole A. Andreassen, Danielle Posthuma, Jordi Clarimón, Mercè Boada, Wiesje M. van der Flier, Alfredo Ramirez, Jean-Charles Lambert, Sven J. van der Lee, and Agustín Ruiz
Subjects: Science
Abstract: Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.
Published: 2021
Full Text: View/download PDF

4. Whole-body MRI within a surveillance program for carriers with clinically actionable germline TP53 variants - the Swedish constitutional TP53 study SWEP53

Author: Meis Omran, Lennart Blomqvist, Yvonne Brandberg, Niklas Pal, Per Kogner, Anne Kinhult Ståhlbom, Emma Tham, and Svetlana Bajalica-Lagercrantz
Subjects: LiFraumeni syndrome, Germline TP53 mutation, Hereditary breast cancer, Pathological variant, Surveillance program, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Genetics, QH426-470
Abstract: Abstract Background The current guidelines in Sweden regarding individuals with a clinically actionable (i.e. pathogenic or likely pathogenic) germline TP53 variant recommend patients to take part of the national Swedish P53 Study (SWEP53). Methods The study comprises a patient registry (mandatory for all participants) and three optional parts: a biobank, a surveillance program and a psychosocial evaluation of the surveillance. All known adult eligible carriers regardless of age are offered to take part of the surveillance program offering MRI yearly of the whole-body, breast, and brain as well as breast ultrasound. A special surveillance program is offered for individuals 15–18 years old with a 50% risk of being a mutation carrier or with a verified TP53 variation, includes ultrasound of the abdomen and urine corticosteroid profiles. Clinically motivated further examinations are performed upon need. The national inclusion is performed through the six clinical genetic units in Sweden at Umeå, Uppsala, Stockholm, Gothenburg, Linköping and Lund, and the surveillance is mainly performed through the oncology clinics. Results To date, a total of 41 adults and 11 children have been included in the study. Conclusions The SWEP53 is the first structured national surveillance program including radiological and clinical routines for TP53 mutation carriers in the Scandinavian setting. The aim of this publication is to present and describe the ongoing Swedish surveillance study to encourage the initiation of similar studies and to contribute to the knowledge of adequate clinical handling of these cancer prone families. Trial registration Trial registration number: ISRCTN13103571, retrospectively registered on 14/10/2019.
Published: 2020
Full Text: View/download PDF

5. Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study

Author: Steinunn Thordardottir, Elena Rodriguez-Vieitez, Ove Almkvist, Daniel Ferreira, Laure Saint-Aubert, Anne Kinhult-Ståhlbom, Håkan Thonberg, Michael Schöll, Eric Westman, Anders Wall, Maria Eriksdotter, Henrik Zetterberg, Kaj Blennow, Agneta Nordberg, and Caroline Graff
Subjects: Autosomal dominant Alzheimer’s disease, CSF, [18F]fluorodeoxyglucose PET, [11C]Pittsburgh compound B PET, Reduced penetrance, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background The range of onset ages within some PSEN1 families is wide, and a few cases of reduced penetrance of PSEN1 mutations have been reported. However, published data on reduced penetrance have been limited to clinical histories, often collected retrospectively and lacking biomarker information. We present a case of reduced penetrance of the PSEN1 H163Y mutation in a carrier prospectively followed for 22 years. Methods Two brothers (A and B), both carriers of the H163Y mutation, were followed between 1995 and 2017. They underwent repeated clinical evaluations, neuropsychological assessments, and cerebrospinal fluid analyses, as well as brain imaging examinations with structural magnetic resonance, [18F]fluorodeoxyglucose positron emission tomography, and [11C]Pittsburgh compound B positron emission tomography. Results Brother A was followed between 44 and 64 years of age. Cognitive symptoms due to Alzheimer’s disease set in at the age of 54. Gradual worsening of symptoms resulted in admittance to a nursing home owing to dependence on others for all activities of daily living. He showed a curvilinear decline in cognitive function on neuropsychological tests, and changes on magnetic resonance imaging, positron emission tomography, and biomarkers in the cerebrospinal fluid supported a clinical diagnosis of Alzheimer’s disease. Brother A died at the age of 64 and fulfilled the criteria for definitive Alzheimer’s disease according to neuropathological examination results. Brother B was followed between the ages of 43 and 65 and showed no cognitive deterioration on repeated neuropsychological test occasions. In addition, no biomarker evidence of Alzheimer’s disease pathology was detected, either on imaging examinations or in cerebrospinal fluid. Conclusions The average (SD) age of symptom onset for PSEN1 H163Y is 51 ± 7 years according to previous studies. However, we present a case of a biomarker-verified reduction in penetrance in a mutation carrier who was still symptom-free at the age of 65. This suggests that other genetic, epigenetic, and/or environmental factors modify the onset age.
Published: 2018
Full Text: View/download PDF

6. Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores (Nature Communications, (2021), 12, 1, (3417), 10.1038/s41467-021-22491-8)

Author: de Rojas, I. Moreno-Grau, S. Tesi, N. Grenier-Boley, B. Andrade, V. Jansen, I.E. Pedersen, N.L. Stringa, N. Zettergren, A. Hernández, I. Montrreal, L. Antúnez, C. Antonell, A. Tankard, R.M. Bis, J.C. Sims, R. Bellenguez, C. Quintela, I. González-Perez, A. Calero, M. Franco-Macías, E. Macías, J. Blesa, R. Cervera-Carles, L. Menéndez-González, M. Frank-García, A. Royo, J.L. Moreno, F. Huerto Vilas, R. Baquero, M. Diez-Fairen, M. Lage, C. García-Madrona, S. García-González, P. Alarcón-Martín, E. Valero, S. Sotolongo-Grau, O. Ullgren, A. Naj, A.C. Lemstra, A.W. Benaque, A. Pérez-Cordón, A. Benussi, A. Rábano, A. Padovani, A. Squassina, A. de Mendonça, A. Arias Pastor, A. Kok, A.A.L. Meggy, A. Pastor, A.B. Espinosa, A. Corma-Gómez, A. Martín Montes, A. Sanabria, Á. DeStefano, A.L. Schneider, A. Haapasalo, A. Kinhult Ståhlbom, A. Tybjærg-Hansen, A. Hartmann, A.M. Spottke, A. Corbatón-Anchuelo, A. Rongve, A. Borroni, B. Arosio, B. Nacmias, B. Nordestgaard, B.G. Kunkle, B.W. Charbonnier, C. Abdelnour, C. Masullo, C. Martínez Rodríguez, C. Muñoz-Fernandez, C. Dufouil, C. Graff, C. Ferreira, C.B. Chillotti, C. Reynolds, C.A. Fenoglio, C. Van Broeckhoven, C. Clark, C. Pisanu, C. Satizabal, C.L. Holmes, C. Buiza-Rueda, D. Aarsland, D. Rujescu, D. Alcolea, D. Galimberti, D. Wallon, D. Seripa, D. Grünblatt, E. Dardiotis, E. Düzel, E. Scarpini, E. Conti, E. Rubino, E. Gelpi, E. Rodriguez-Rodriguez, E. Duron, E. Boerwinkle, E. Ferri, E. Tagliavini, F. Küçükali, F. Pasquier, F. Sanchez-Garcia, F. Mangialasche, F. Jessen, F. Nicolas, G. Selbæk, G. Ortega, G. Chêne, G. Hadjigeorgiou, G. Rossi, G. Spalletta, G. Giaccone, G. Grande, G. Binetti, G. Papenberg, G. Hampel, H. Bailly, H. Zetterberg, H. Soininen, H. Karlsson, I.K. Alvarez, I. Appollonio, I. Giegling, I. Skoog, I. Saltvedt, I. Rainero, I. Rosas Allende, I. Hort, J. Diehl-Schmid, J. Van Dongen, J. Vidal, J.-S. Lehtisalo, J. Wiltfang, J. Thomassen, J.Q. Kornhuber, J. Haines, J.L. Vogelgsang, J. Pineda, J.A. Fortea, J. Popp, J. D and de Rojas, I. Moreno-Grau, S. Tesi, N. Grenier-Boley, B. Andrade, V. Jansen, I.E. Pedersen, N.L. Stringa, N. Zettergren, A. Hernández, I. Montrreal, L. Antúnez, C. Antonell, A. Tankard, R.M. Bis, J.C. Sims, R. Bellenguez, C. Quintela, I. González-Perez, A. Calero, M. Franco-Macías, E. Macías, J. Blesa, R. Cervera-Carles, L. Menéndez-González, M. Frank-García, A. Royo, J.L. Moreno, F. Huerto Vilas, R. Baquero, M. Diez-Fairen, M. Lage, C. García-Madrona, S. García-González, P. Alarcón-Martín, E. Valero, S. Sotolongo-Grau, O. Ullgren, A. Naj, A.C. Lemstra, A.W. Benaque, A. Pérez-Cordón, A. Benussi, A. Rábano, A. Padovani, A. Squassina, A. de Mendonça, A. Arias Pastor, A. Kok, A.A.L. Meggy, A. Pastor, A.B. Espinosa, A. Corma-Gómez, A. Martín Montes, A. Sanabria, Á. DeStefano, A.L. Schneider, A. Haapasalo, A. Kinhult Ståhlbom, A. Tybjærg-Hansen, A. Hartmann, A.M. Spottke, A. Corbatón-Anchuelo, A. Rongve, A. Borroni, B. Arosio, B. Nacmias, B. Nordestgaard, B.G. Kunkle, B.W. Charbonnier, C. Abdelnour, C. Masullo, C. Martínez Rodríguez, C. Muñoz-Fernandez, C. Dufouil, C. Graff, C. Ferreira, C.B. Chillotti, C. Reynolds, C.A. Fenoglio, C. Van Broeckhoven, C. Clark, C. Pisanu, C. Satizabal, C.L. Holmes, C. Buiza-Rueda, D. Aarsland, D. Rujescu, D. Alcolea, D. Galimberti, D. Wallon, D. Seripa, D. Grünblatt, E. Dardiotis, E. Düzel, E. Scarpini, E. Conti, E. Rubino, E. Gelpi, E. Rodriguez-Rodriguez, E. Duron, E. Boerwinkle, E. Ferri, E. Tagliavini, F. Küçükali, F. Pasquier, F. Sanchez-Garcia, F. Mangialasche, F. Jessen, F. Nicolas, G. Selbæk, G. Ortega, G. Chêne, G. Hadjigeorgiou, G. Rossi, G. Spalletta, G. Giaccone, G. Grande, G. Binetti, G. Papenberg, G. Hampel, H. Bailly, H. Zetterberg, H. Soininen, H. Karlsson, I.K. Alvarez, I. Appollonio, I. Giegling, I. Skoog, I. Saltvedt, I. Rainero, I. Rosas Allende, I. Hort, J. Diehl-Schmid, J. Van Dongen, J. Vidal, J.-S. Lehtisalo, J. Wiltfang, J. Thomassen, J.Q. Kornhuber, J. Haines, J.L. Vogelgsang, J. Pineda, J.A. Fortea, J. Popp, J. D
Abstract: The original version of this Article omitted from the author list the 212th author Patrizia Mecocci, who is from the Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy. Consequently, the “Sample Contribution” section of Author Contributions was updated to add “P.M” between “P.D.” and “R.C.”. Additionally, the original version of this Article contained the incorrect affiliation for author Patrick Gavin Kehoe, which incorrectly read “German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany”. The correct version replaces this affiliation with “Bristol Medical School (THS), University of Bristol, Southmead Hospital, Bristol, UK”. This has been corrected in both the PDF and HTML versions of the Article. © The Author(s) 2023.
Published: 2023

7. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

Author: de Rojas, I, Moreno-Grau, S, Tesi, N, Grenier-Boley, B, Andrade, V, Jansen, I, Pedersen, N, Stringa, N, Zettergren, A, Hernández, I, Montrreal, L, Antúnez, C, Antonell, A, Tankard, R, Bis, J, Sims, R, Bellenguez, C, Quintela, I, González-Perez, A, Calero, M, Franco-Macías, E, Macías, J, Blesa, R, Cervera-Carles, L, Menéndez-González, M, Frank-García, A, Royo, J, Moreno, F, Huerto Vilas, R, Baquero, M, Diez-Fairen, M, Lage, C, García-Madrona, S, García-González, P, Alarcón-Martín, E, Valero, S, Sotolongo-Grau, O, Ullgren, A, Naj, A, Lemstra, A, Benaque, A, Pérez-Cordón, A, Benussi, A, Rábano, A, Padovani, A, Squassina, A, de Mendonça, A, Arias Pastor, A, Kok, A, Meggy, A, Pastor, A, Espinosa, A, Corma-Gómez, A, Martín Montes, A, Sanabria, Á, Destefano, A, Schneider, A, Haapasalo, A, Kinhult Ståhlbom, A, Tybjærg-Hansen, A, Hartmann, A, Spottke, A, Corbatón-Anchuelo, A, Rongve, A, Borroni, B, Arosio, B, Nacmias, B, Nordestgaard, B, Kunkle, B, Charbonnier, C, Abdelnour, C, Masullo, C, Martínez Rodríguez, C, Muñoz-Fernandez, C, Dufouil, C, Graff, C, Ferreira, C, Chillotti, C, Reynolds, C, Fenoglio, C, Van Broeckhoven, C, Clark, C, Pisanu, C, Satizabal, C, Holmes, C, Buiza-Rueda, D, Aarsland, D, Rujescu, D, Alcolea, D, Galimberti, D, Wallon, D, Seripa, D, Grünblatt, E, Dardiotis, E, Düzel, E, Scarpini, E, Conti, E, Rubino, E, Gelpi, E, Rodriguez-Rodriguez, E, Duron, E, Boerwinkle, E, Ferri, E, Tagliavini, F, Küçükali, F, Pasquier, F, Sanchez-Garcia, F, Mangialasche, F, Jessen, F, Nicolas, G, Selbæk, G, Ortega, G, Chêne, G, Hadjigeorgiou, G, Rossi, G, Spalletta, G, Giaccone, G, Grande, G, Binetti, G, Papenberg, G, Hampel, H, Bailly, H, Zetterberg, H, Soininen, H, Karlsson, I, Alvarez, I, Appollonio, I, Giegling, I, Skoog, I, Saltvedt, I, Rainero, I, Rosas Allende, I, Hort, J, Diehl-Schmid, J, Van Dongen, J, Vidal, J, Lehtisalo, J, Wiltfang, J, Thomassen, J, Kornhuber, J, Haines, J, Vogelgsang, J, Pineda, J, Fortea, J, Popp, J, Deckert, J, Buerger, K, Morgan, K, Fließbach, K, Sleegers, K, Molina-Porcel, L, Kilander, L, Weinhold, L, Farrer, L, Wang, L, Kleineidam, L, Farotti, L, Parnetti, L, Tremolizzo, L, Hausner, L, Benussi, L, Froelich, L, Ikram, M, Deniz-Naranjo, M, Tsolaki, M, Rosende-Roca, M, Löwenmark, M, Hulsman, M, Spallazzi, M, Pericak-Vance, M, Esiri, M, Bernal Sánchez-Arjona, M, Dalmasso, M, Martínez-Larrad, M, Arcaro, M, Nöthen, M, Fernández-Fuertes, M, Dichgans, M, Ingelsson, M, Herrmann, M, Scherer, M, Vyhnalek, M, Kosmidis, M, Yannakoulia, M, Schmid, M, Ewers, M, Heneka, M, Wagner, M, Scamosci, M, Kivipelto, M, Hiltunen, M, Zulaica, M, Alegret, M, Fornage, M, Roberto, N, van Schoor, N, Seidu, N, Banaj, N, Armstrong, N, Scarmeas, N, Scherbaum, N, Goldhardt, O, Hanon, O, Peters, O, Skrobot, O, Quenez, O, Lerch, O, Bossù, P, Caffarra, P, Dionigi Rossi, P, Sakka, P, Hoffmann, P, Holmans, P, Fischer, P, Riederer, P, Yang, Q, Marshall, R, Kalaria, R, Mayeux, R, Vandenberghe, R, Cecchetti, R, Ghidoni, R, Frikke-Schmidt, R, Sorbi, S, Hägg, S, Engelborghs, S, Helisalmi, S, Botne Sando, S, Kern, S, Archetti, S, Boschi, S, Fostinelli, S, Gil, S, Mendoza, S, Mead, S, Ciccone, S, Djurovic, S, Heilmann-Heimbach, S, Riedel-Heller, S, Kuulasmaa, T, Del Ser, T, Lebouvier, T, Polak, T, Ngandu, T, Grimmer, T, Bessi, V, Escott-Price, V, Giedraitis, V, Deramecourt, V, Maier, W, Jian, X, Pijnenburg, Y, Andreoni, S, Ferrarese, C, Sala, G, Zoia, C, Kehoe, P, Garcia-Ribas, G, Sánchez-Juan, P, Pastor, P, Pérez-Tur, J, Piñol-Ripoll, G, Lopez de Munain, A, García-Alberca, J, Bullido, M, Álvarez, V, Lleó, A, Real, L, Mir, P, Medina, M, Scheltens, P, Holstege, H, Marquié, M, Sáez, M, Carracedo, Á, Amouyel, P, Schellenberg, G, Williams, J, Seshadri, S, van Duijn, C, Mather, K, Sánchez-Valle, R, Serrano-Ríos, M, Orellana, A, Tárraga, L, Blennow, K, Huisman, M, Andreassen, O, Posthuma, D, Clarimón, J, Boada, M, van der Flier, W, Ramirez, A, Lambert, J, van der Lee, S, Ruiz, A, de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E, Pedersen, Nancy L, Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M, Bis, Joshua C, Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C, Lemstra, Afina W, Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A L, Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anas, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L, Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M, Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G, Kunkle, Brian W, Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B, Chillotti, Caterina, Reynolds, Chandra A, Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L, Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K, Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L, Vogelgsang, Jonathan, Pineda, Juan A, Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A, Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M Arfan, Deniz-Naranjo, M Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A, Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M, Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J, Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H, Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T, Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M, Seidu, Nazib M, Banaj, Nerisa, Armstrong, Nicola J, Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Hoffmann, Per, Holmans, Peter A, Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N, Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, Del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A L, Andreoni, Simona, Ferrarese, Carlo, Sala Gessica, Zoia, Chiara Paola, Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J, Álvarez, Victoria, Lleó, Alberto, Real, Luis M, Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D, Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M, Mather, Karen A, Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A, Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M, Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J, Ruiz, Agustín, de Rojas, I, Moreno-Grau, S, Tesi, N, Grenier-Boley, B, Andrade, V, Jansen, I, Pedersen, N, Stringa, N, Zettergren, A, Hernández, I, Montrreal, L, Antúnez, C, Antonell, A, Tankard, R, Bis, J, Sims, R, Bellenguez, C, Quintela, I, González-Perez, A, Calero, M, Franco-Macías, E, Macías, J, Blesa, R, Cervera-Carles, L, Menéndez-González, M, Frank-García, A, Royo, J, Moreno, F, Huerto Vilas, R, Baquero, M, Diez-Fairen, M, Lage, C, García-Madrona, S, García-González, P, Alarcón-Martín, E, Valero, S, Sotolongo-Grau, O, Ullgren, A, Naj, A, Lemstra, A, Benaque, A, Pérez-Cordón, A, Benussi, A, Rábano, A, Padovani, A, Squassina, A, de Mendonça, A, Arias Pastor, A, Kok, A, Meggy, A, Pastor, A, Espinosa, A, Corma-Gómez, A, Martín Montes, A, Sanabria, Á, Destefano, A, Schneider, A, Haapasalo, A, Kinhult Ståhlbom, A, Tybjærg-Hansen, A, Hartmann, A, Spottke, A, Corbatón-Anchuelo, A, Rongve, A, Borroni, B, Arosio, B, Nacmias, B, Nordestgaard, B, Kunkle, B, Charbonnier, C, Abdelnour, C, Masullo, C, Martínez Rodríguez, C, Muñoz-Fernandez, C, Dufouil, C, Graff, C, Ferreira, C, Chillotti, C, Reynolds, C, Fenoglio, C, Van Broeckhoven, C, Clark, C, Pisanu, C, Satizabal, C, Holmes, C, Buiza-Rueda, D, Aarsland, D, Rujescu, D, Alcolea, D, Galimberti, D, Wallon, D, Seripa, D, Grünblatt, E, Dardiotis, E, Düzel, E, Scarpini, E, Conti, E, Rubino, E, Gelpi, E, Rodriguez-Rodriguez, E, Duron, E, Boerwinkle, E, Ferri, E, Tagliavini, F, Küçükali, F, Pasquier, F, Sanchez-Garcia, F, Mangialasche, F, Jessen, F, Nicolas, G, Selbæk, G, Ortega, G, Chêne, G, Hadjigeorgiou, G, Rossi, G, Spalletta, G, Giaccone, G, Grande, G, Binetti, G, Papenberg, G, Hampel, H, Bailly, H, Zetterberg, H, Soininen, H, Karlsson, I, Alvarez, I, Appollonio, I, Giegling, I, Skoog, I, Saltvedt, I, Rainero, I, Rosas Allende, I, Hort, J, Diehl-Schmid, J, Van Dongen, J, Vidal, J, Lehtisalo, J, Wiltfang, J, Thomassen, J, Kornhuber, J, Haines, J, Vogelgsang, J, Pineda, J, Fortea, J, Popp, J, Deckert, J, Buerger, K, Morgan, K, Fließbach, K, Sleegers, K, Molina-Porcel, L, Kilander, L, Weinhold, L, Farrer, L, Wang, L, Kleineidam, L, Farotti, L, Parnetti, L, Tremolizzo, L, Hausner, L, Benussi, L, Froelich, L, Ikram, M, Deniz-Naranjo, M, Tsolaki, M, Rosende-Roca, M, Löwenmark, M, Hulsman, M, Spallazzi, M, Pericak-Vance, M, Esiri, M, Bernal Sánchez-Arjona, M, Dalmasso, M, Martínez-Larrad, M, Arcaro, M, Nöthen, M, Fernández-Fuertes, M, Dichgans, M, Ingelsson, M, Herrmann, M, Scherer, M, Vyhnalek, M, Kosmidis, M, Yannakoulia, M, Schmid, M, Ewers, M, Heneka, M, Wagner, M, Scamosci, M, Kivipelto, M, Hiltunen, M, Zulaica, M, Alegret, M, Fornage, M, Roberto, N, van Schoor, N, Seidu, N, Banaj, N, Armstrong, N, Scarmeas, N, Scherbaum, N, Goldhardt, O, Hanon, O, Peters, O, Skrobot, O, Quenez, O, Lerch, O, Bossù, P, Caffarra, P, Dionigi Rossi, P, Sakka, P, Hoffmann, P, Holmans, P, Fischer, P, Riederer, P, Yang, Q, Marshall, R, Kalaria, R, Mayeux, R, Vandenberghe, R, Cecchetti, R, Ghidoni, R, Frikke-Schmidt, R, Sorbi, S, Hägg, S, Engelborghs, S, Helisalmi, S, Botne Sando, S, Kern, S, Archetti, S, Boschi, S, Fostinelli, S, Gil, S, Mendoza, S, Mead, S, Ciccone, S, Djurovic, S, Heilmann-Heimbach, S, Riedel-Heller, S, Kuulasmaa, T, Del Ser, T, Lebouvier, T, Polak, T, Ngandu, T, Grimmer, T, Bessi, V, Escott-Price, V, Giedraitis, V, Deramecourt, V, Maier, W, Jian, X, Pijnenburg, Y, Andreoni, S, Ferrarese, C, Sala, G, Zoia, C, Kehoe, P, Garcia-Ribas, G, Sánchez-Juan, P, Pastor, P, Pérez-Tur, J, Piñol-Ripoll, G, Lopez de Munain, A, García-Alberca, J, Bullido, M, Álvarez, V, Lleó, A, Real, L, Mir, P, Medina, M, Scheltens, P, Holstege, H, Marquié, M, Sáez, M, Carracedo, Á, Amouyel, P, Schellenberg, G, Williams, J, Seshadri, S, van Duijn, C, Mather, K, Sánchez-Valle, R, Serrano-Ríos, M, Orellana, A, Tárraga, L, Blennow, K, Huisman, M, Andreassen, O, Posthuma, D, Clarimón, J, Boada, M, van der Flier, W, Ramirez, A, Lambert, J, van der Lee, S, Ruiz, A, de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E, Pedersen, Nancy L, Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M, Bis, Joshua C, Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C, Lemstra, Afina W, Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A L, Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anas, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L, Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M, Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G, Kunkle, Brian W, Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B, Chillotti, Caterina, Reynolds, Chandra A, Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L, Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K, Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L, Vogelgsang, Jonathan, Pineda, Juan A, Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A, Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M Arfan, Deniz-Naranjo, M Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A, Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M, Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J, Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H, Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T, Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M, Seidu, Nazib M, Banaj, Nerisa, Armstrong, Nicola J, Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Hoffmann, Per, Holmans, Peter A, Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N, Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, Del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A L, Andreoni, Simona, Ferrarese, Carlo, Sala Gessica, Zoia, Chiara Paola, Kehoe, Patrick Gavin, Garcia-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J, Álvarez, Victoria, Lleó, Alberto, Real, Luis M, Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D, Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M, Mather, Karen A, Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A, Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M, Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J, and Ruiz, Agustín
Abstract: Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.
Published: 2021

8. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author: de Rojas, I. Moreno-Grau, S. Tesi, N. Grenier-Boley, B. Andrade, V. Jansen, I.E. Pedersen, N.L. Stringa, N. Zettergren, A. Hernández, I. Montrreal, L. Antúnez, C. Antonell, A. Tankard, R.M. Bis, J.C. Sims, R. Bellenguez, C. Quintela, I. González-Perez, A. Calero, M. Franco-Macías, E. Macías, J. Blesa, R. Cervera-Carles, L. Menéndez-González, M. Frank-García, A. Royo, J.L. Moreno, F. Huerto Vilas, R. Baquero, M. Diez-Fairen, M. Lage, C. García-Madrona, S. García-González, P. Alarcón-Martín, E. Valero, S. Sotolongo-Grau, O. Ullgren, A. Naj, A.C. Lemstra, A.W. Benaque, A. Pérez-Cordón, A. Benussi, A. Rábano, A. Padovani, A. Squassina, A. de Mendonça, A. Arias Pastor, A. Kok, A.A.L. Meggy, A. Pastor, A.B. Espinosa, A. Corma-Gómez, A. Martín Montes, A. Sanabria, Á. DeStefano, A.L. Schneider, A. Haapasalo, A. Kinhult Ståhlbom, A. Tybjærg-Hansen, A. Hartmann, A.M. Spottke, A. Corbatón-Anchuelo, A. Rongve, A. Borroni, B. Arosio, B. Nacmias, B. Nordestgaard, B.G. Kunkle, B.W. Charbonnier, C. Abdelnour, C. Masullo, C. Martínez Rodríguez, C. Muñoz-Fernandez, C. Dufouil, C. Graff, C. Ferreira, C.B. Chillotti, C. Reynolds, C.A. Fenoglio, C. Van Broeckhoven, C. Clark, C. Pisanu, C. Satizabal, C.L. Holmes, C. Buiza-Rueda, D. Aarsland, D. Rujescu, D. Alcolea, D. Galimberti, D. Wallon, D. Seripa, D. Grünblatt, E. Dardiotis, E. Düzel, E. Scarpini, E. Conti, E. Rubino, E. Gelpi, E. Rodriguez-Rodriguez, E. Duron, E. Boerwinkle, E. Ferri, E. Tagliavini, F. Küçükali, F. Pasquier, F. Sanchez-Garcia, F. Mangialasche, F. Jessen, F. Nicolas, G. Selbæk, G. Ortega, G. Chêne, G. Hadjigeorgiou, G. Rossi, G. Spalletta, G. Giaccone, G. Grande, G. Binetti, G. Papenberg, G. Hampel, H. Bailly, H. Zetterberg, H. Soininen, H. Karlsson, I.K. Alvarez, I. Appollonio, I. Giegling, I. Skoog, I. Saltvedt, I. Rainero, I. Rosas Allende, I. Hort, J. Diehl-Schmid, J. Van Dongen, J. Vidal, J.-S. Lehtisalo, J. Wiltfang, J. Thomassen, J.Q. Kornhuber, J. Haines, J.L. Vogelgsang, J. Pineda, J.A. Fortea, J. Popp, J. Deckert, J. Buerger, K. Morgan, K. Fließbach, K. Sleegers, K. Molina-Porcel, L. Kilander, L. Weinhold, L. Farrer, L.A. Wang, L.-S. Kleineidam, L. Farotti, L. Parnetti, L. Tremolizzo, L. Hausner, L. Benussi, L. Froelich, L. Ikram, M.A. Deniz-Naranjo, M.C. Tsolaki, M. Rosende-Roca, M. Löwenmark, M. Hulsman, M. Spallazzi, M. Pericak-Vance, M.A. Esiri, M. Bernal Sánchez-Arjona, M. Dalmasso, M.C. Martínez-Larrad, M.T. Arcaro, M. Nöthen, M.M. Fernández-Fuertes, M. Dichgans, M. Ingelsson, M. Herrmann, M.J. Scherer, M. Vyhnalek, M. Kosmidis, M.H. Yannakoulia, M. Schmid, M. Ewers, M. Heneka, M.T. Wagner, M. Scamosci, M. Kivipelto, M. Hiltunen, M. Zulaica, M. Alegret, M. Fornage, M. Roberto, N. van Schoor, N.M. Seidu, N.M. Banaj, N. Armstrong, N.J. Scarmeas, N. Scherbaum, N. Goldhardt, O. Hanon, O. Peters, O. Skrobot, O.A. Quenez, O. Lerch, O. Bossù, P. Caffarra, P. Dionigi Rossi, P. Sakka, P. Hoffmann, P. Holmans, P.A. Fischer, P. Riederer, P. Yang, Q. Marshall, R. Kalaria, R.N. Mayeux, R. Vandenberghe, R. Cecchetti, R. Ghidoni, R. Frikke-Schmidt, R. Sorbi, S. Hägg, S. Engelborghs, S. Helisalmi, S. Botne Sando, S. Kern, S. Archetti, S. Boschi, S. Fostinelli, S. Gil, S. Mendoza, S. Mead, S. Ciccone, S. Djurovic, S. Heilmann-Heimbach, S. Riedel-Heller, S. Kuulasmaa, T. del Ser, T. Lebouvier, T. Polak, T. Ngandu, T. Grimmer, T. Bessi, V. Escott-Price, V. Giedraitis, V. Deramecourt, V. Maier, W. Jian, X. Pijnenburg, Y.A.L. Smith, A.D. Saenz, A. Bizzarro, A. Lauria, A. Vacca, A. Solomon, A. Anastasiou, A. Richardson, A. Boland, A. Koivisto, A. Daniele, A. Greco, A. Marianthi, A. McGuinness, B. Fin, B. Ferrari, C. Custodero, C. Ferrarese, C. Ingino, C. Mangone, C. Reyes Toso, C. Martínez, C. Cuesta, C. Muchnik, C. Joachim, C. Ortiz, C. Besse, C. Johansson, C. Zoia, C.P. Laske, C. Anastasiou, C. Palacio, D.L. Politis, D.G. Janowitz, D. Craig, D. Mann, D.M. Neary, D. Jürgen, D. Daian, D. Belezhanska, D. Kohler, E. Castaño, E.M. Koutsouraki, E. Chipi, E. De Roeck, E. Costantini, E. Vardy, E.R.L.C. Piras, F. Roveta, F. Piras, F. Prestia, F.A. Assogna, F. Salani, F. Sala, G. Lacidogna, G. Novack, G. Wilcock, G. Thonberg, H. Kölsch, H. Weber, H. Boecker, H. Etchepareborda, I. Piaceri, I. Tuomilehto, J. Lindström, J. Laczo, J. Johnston, J. Deleuze, J.-F. Harris, J. Schott, J.M. Priller, J. Bacha, J.I. Snowden, J. Lisso, J. Mihova, K.Y. Traykov, L. Morelli, L. Brusco, L.I. Rainer, M. Takalo, M. Bjerke, M. Del Zompo, M. Serpente, M. Sanchez Abalos, M. Rios, M. Peltonen, M. Herrman, M.J. Kosmidis, M.H. Kohler, M. Rojo, M. Jones, M. Orsini, M. Medel, N. Olivar, N. Fox, N.C. Salvadori, N. Hooper, N.M. Galeano, P. Solis, P. Bastiani, P. Mecocci, P. Passmore, P. Heun, R. Antikainen, R. Olaso, R. Perneczky, R. Germani, S. López-García, S. Love, S. Mehrabian, S. Bagnoli, S. Kochen, S. Andreoni, S. Teipel, S. Todd, S. Pickering-Brown, S. Natunen, T. Tegos, T. Laatikainen, T. Strandberg, T. Polvikoski, T.M. Matoska, V. Ciullo, V. Cores, V. Solfrizzi, V. Lisetti, V. Sevillano, Z. Abdelnour, C. Aguilera, N. Alarcon, E. Alegret, M. Benaque, A. Boada, M. Buendia, M. Cañabate, P. Carracedo, A. Corbatón-Anchuelo, A. Diego, S. Espinosa, A. Gailhajenet, A. Gil, S. Guitart, M. Hernández, I. Ibarria, M. Lafuente, A. Macias, J. Maroñas, O. Martín, E. Martínez, M.T. Marquié, M. Mauleón, A. Montrreal, L. Moreno-Grau, S. Moreno, M. Orellana, A. Ortega, G. Pancho, A. Pelejá, E. Pérez-Cordon, A. Pineda, J.A. Preckler, S. Quintela, I. Real, L.M. Rosende-Roca, M. Ruiz, A. Sáez, M.E. Sanabria, A. Serrano-Rios, M. Sotolongo-Grau, O. Tárraga, L. Valero, S. Vargas, L. Adarmes-Gómez, A.D. Alarcón-Martín, E. Alonso, M.D. Álvarez, I. Álvarez, V. Amer-Ferrer, G. Antequera, M. Antúnez, C. Baquero, M. Bernal, M. Blesa, R. Boada, M. Buiza-Rueda, D. Bullido, M.J. Burguera, J.A. Calero, M. Carrillo, F. Carrión-Claro, M. Casajeros, M.J. Clarimón, J. Cruz-Gamero, J.M. de Pancorbo, M.M. del Ser, T. Diez-Fairen, M. Escuela, R. Garrote-Espina, L. Fortea, J. Franco-Macías, E. Frank-García, A. García-Alberca, J.M. Garcia Madrona, S. Garcia-Ribas, G. Gómez-Garre, P. Hernández, I. Hevilla, S. Jesús, S. Labrador Espinosa, M.A. Lage, C. Legaz, A. Lleó, A. Lopez de Munain, A. López-García, S. Macias-García, D. Manzanares, S. Marín, M. Marín-Muñoz, J. Marín, T. Marquié, M. Martín Montes, A. Martínez, B. Martínez, C. Martínez, V. Martínez-Lage Álvarez, P. Medina, M. Mendioroz Iriarte, M. Mir, P. Molinuevo, J.L. Pastor, P. Pérez Tur, J. Periñán-Tocino, T. Pineda-Sanchez, R. Piñol-Ripoll, G. Rábano, A. Real de Asúa, D. Rodrigo, S. Rodríguez-Rodríguez, E. Royo, J.L. Ruiz, A. Sanchez del Valle Díaz, R. Sánchez-Juan, P. Sastre, I. Valero, S. Vicente, M.P. Vigo-Ortega, R. Vivancos, L. Macleod, C. McCracken, C. Brayne, C. Bresner, C. Grozeva, D. Bellou, E. Sommerville, E.W. Matthews, F. Leonenko, G. Menzies, G. Windle, G. Harwood, J. Phillips, J. Bennett, K. Luckuck, L. Clare, L. Woods, R. Saad, S. Burholt, V. Jansen, I.E. Rongve, A. Kehoe, P.G. Garcia-Ribas, G. Sánchez-Juan, P. Pastor, P. Pérez-Tur, J. Piñol-Ripoll, G. Lopez de Munain, A. García-Alberca, J.M. Bullido, M.J. Álvarez, V. Lleó, A. Real, L.M. Scheltens, P. Holstege, H. Marquié, M. Sáez, M.E. Carracedo, Á. Amouyel, P. Schellenberg, G.D. Williams, J. Seshadri, S. van Duijn, C.M. Mather, K.A. Sánchez-Valle, R. Serrano-Ríos, M. Orellana, A. Tárraga, L. Blennow, K. Huisman, M. Andreassen, O.A. Posthuma, D. Clarimón, J. Boada, M. van der Flier, W.M. Ramirez, A. Lambert, J.-C. van der Lee, S.J. Ruiz, A. EADB contributors The GR@ACE study group DEGESCO consortium IGAP (ADGC, CHARGE, EADI, GERAD) PGC-ALZ consortia
Abstract: Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
Published: 2021

9. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author: de Rojas, I. Moreno-Grau, S. Tesi, N. Grenier-Boley, B. Andrade, V. Jansen, I.E. Pedersen, N.L. Stringa, N. Zettergren, A. Hernández, I. Montrreal, L. Antúnez, C. Antonell, A. Tankard, R.M. Bis, J.C. Sims, R. Bellenguez, C. Quintela, I. González-Perez, A. Calero, M. Franco-Macías, E. Macías, J. Blesa, R. Cervera-Carles, L. Menéndez-González, M. Frank-García, A. Royo, J.L. Moreno, F. Huerto Vilas, R. Baquero, M. Diez-Fairen, M. Lage, C. García-Madrona, S. García-González, P. Alarcón-Martín, E. Valero, S. Sotolongo-Grau, O. Ullgren, A. Naj, A.C. Lemstra, A.W. Benaque, A. Pérez-Cordón, A. Benussi, A. Rábano, A. Padovani, A. Squassina, A. de Mendonça, A. Arias Pastor, A. Kok, A.A.L. Meggy, A. Pastor, A.B. Espinosa, A. Corma-Gómez, A. Martín Montes, A. Sanabria, Á. DeStefano, A.L. Schneider, A. Haapasalo, A. Kinhult Ståhlbom, A. Tybjærg-Hansen, A. Hartmann, A.M. Spottke, A. Corbatón-Anchuelo, A. Rongve, A. Borroni, B. Arosio, B. Nacmias, B. Nordestgaard, B.G. Kunkle, B.W. Charbonnier, C. Abdelnour, C. Masullo, C. Martínez Rodríguez, C. Muñoz-Fernandez, C. Dufouil, C. Graff, C. Ferreira, C.B. Chillotti, C. Reynolds, C.A. Fenoglio, C. Van Broeckhoven, C. Clark, C. Pisanu, C. Satizabal, C.L. Holmes, C. Buiza-Rueda, D. Aarsland, D. Rujescu, D. Alcolea, D. Galimberti, D. Wallon, D. Seripa, D. Grünblatt, E. Dardiotis, E. Düzel, E. Scarpini, E. Conti, E. Rubino, E. Gelpi, E. Rodriguez-Rodriguez, E. Duron, E. Boerwinkle, E. Ferri, E. Tagliavini, F. Küçükali, F. Pasquier, F. Sanchez-Garcia, F. Mangialasche, F. Jessen, F. Nicolas, G. Selbæk, G. Ortega, G. Chêne, G. Hadjigeorgiou, G. Rossi, G. Spalletta, G. Giaccone, G. Grande, G. Binetti, G. Papenberg, G. Hampel, H. Bailly, H. Zetterberg, H. Soininen, H. Karlsson, I.K. Alvarez, I. Appollonio, I. Giegling, I. Skoog, I. Saltvedt, I. Rainero, I. Rosas Allende, I. Hort, J. Diehl-Schmid, J. Van Dongen, J. Vidal, J.-S. Lehtisalo, J. Wiltfang, J. Thomassen, J.Q. Kornhuber, J. Haines, J.L. Vogelgsang, J. Pineda, J.A. Fortea, J. Popp, J. D and de Rojas, I. Moreno-Grau, S. Tesi, N. Grenier-Boley, B. Andrade, V. Jansen, I.E. Pedersen, N.L. Stringa, N. Zettergren, A. Hernández, I. Montrreal, L. Antúnez, C. Antonell, A. Tankard, R.M. Bis, J.C. Sims, R. Bellenguez, C. Quintela, I. González-Perez, A. Calero, M. Franco-Macías, E. Macías, J. Blesa, R. Cervera-Carles, L. Menéndez-González, M. Frank-García, A. Royo, J.L. Moreno, F. Huerto Vilas, R. Baquero, M. Diez-Fairen, M. Lage, C. García-Madrona, S. García-González, P. Alarcón-Martín, E. Valero, S. Sotolongo-Grau, O. Ullgren, A. Naj, A.C. Lemstra, A.W. Benaque, A. Pérez-Cordón, A. Benussi, A. Rábano, A. Padovani, A. Squassina, A. de Mendonça, A. Arias Pastor, A. Kok, A.A.L. Meggy, A. Pastor, A.B. Espinosa, A. Corma-Gómez, A. Martín Montes, A. Sanabria, Á. DeStefano, A.L. Schneider, A. Haapasalo, A. Kinhult Ståhlbom, A. Tybjærg-Hansen, A. Hartmann, A.M. Spottke, A. Corbatón-Anchuelo, A. Rongve, A. Borroni, B. Arosio, B. Nacmias, B. Nordestgaard, B.G. Kunkle, B.W. Charbonnier, C. Abdelnour, C. Masullo, C. Martínez Rodríguez, C. Muñoz-Fernandez, C. Dufouil, C. Graff, C. Ferreira, C.B. Chillotti, C. Reynolds, C.A. Fenoglio, C. Van Broeckhoven, C. Clark, C. Pisanu, C. Satizabal, C.L. Holmes, C. Buiza-Rueda, D. Aarsland, D. Rujescu, D. Alcolea, D. Galimberti, D. Wallon, D. Seripa, D. Grünblatt, E. Dardiotis, E. Düzel, E. Scarpini, E. Conti, E. Rubino, E. Gelpi, E. Rodriguez-Rodriguez, E. Duron, E. Boerwinkle, E. Ferri, E. Tagliavini, F. Küçükali, F. Pasquier, F. Sanchez-Garcia, F. Mangialasche, F. Jessen, F. Nicolas, G. Selbæk, G. Ortega, G. Chêne, G. Hadjigeorgiou, G. Rossi, G. Spalletta, G. Giaccone, G. Grande, G. Binetti, G. Papenberg, G. Hampel, H. Bailly, H. Zetterberg, H. Soininen, H. Karlsson, I.K. Alvarez, I. Appollonio, I. Giegling, I. Skoog, I. Saltvedt, I. Rainero, I. Rosas Allende, I. Hort, J. Diehl-Schmid, J. Van Dongen, J. Vidal, J.-S. Lehtisalo, J. Wiltfang, J. Thomassen, J.Q. Kornhuber, J. Haines, J.L. Vogelgsang, J. Pineda, J.A. Fortea, J. Popp, J. D
Abstract: Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
Published: 2021

10. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author: de Rojas, I., Moreno-Grau, S., Tesi, N., Grenier-Boley, B., Andrade, V., Jansen, I.E., Pedersen, N.L., Stringa, N., Zettergren, A., Hernández, I., Montrreal, L., Antúnez, C., Antonell, A., Tankard, R.M., Bis, J.C., Sims, R., Bellenguez, C., Quintela, I., González-Perez, A., Calero, M., Franco-Macías, E., Macías, J., Blesa, R., Cervera-Carles, L., Menéndez-González, M., Frank-García, A., Royo, J.L., Moreno, F., Huerto Vilas, R., Baquero, M., Diez-Fairen, M., Lage, C., García-Madrona, S., García-González, P., Alarcón-Martín, E., Valero, S., Sotolongo-Grau, O., Ullgren, A., Naj, A.C., Lemstra, A.W., Benaque, A., Pérez-Cordón, A., Benussi, A., Rábano, A., Padovani, A., Squassina, A., de Mendonça, A., Arias Pastor, A., Kok, A.A.L., Meggy, A., Pastor, A.B., Espinosa, A., Corma-Gómez, A., Martín Montes, A., Sanabria, Á., DeStefano, A.L., Schneider, A., Haapasalo, A., Kinhult Ståhlbom, A., Tybjærg-Hansen, A., Hartmann, A.M., Spottke, A., Corbatón-Anchuelo, A., Rongve, A., Borroni, B., Arosio, B., Nacmias, B., Nordestgaard, B.G., Kunkle, B.W., Charbonnier, C., Abdelnour, C., Masullo, C., Martínez Rodríguez, C., Muñoz-Fernandez, C., Dufouil, C., Graff, C., Ferreira, C.B., Chillotti, C., Reynolds, C.A., Fenoglio, C., Van Broeckhoven, C., Clark, C., Pisanu, C., Satizabal, C.L., Holmes, C., Buiza-Rueda, D., Aarsland, D., Rujescu, D., Alcolea, D., Galimberti, D., Wallon, D., Seripa, D., Grünblatt, E., Dardiotis, E., Düzel, E., Scarpini, E., Conti, E., Rubino, E., Gelpi, E., Rodriguez-Rodriguez, E., Duron, E., Boerwinkle, E., Ferri, E., Tagliavini, F., Küçükali, F., Pasquier, F., Sanchez-Garcia, F., Mangialasche, F., Jessen, F., Nicolas, G., Selbæk, G., Ortega, G., Chêne, G., Hadjigeorgiou, G., Rossi, G, Spalletta, G., Giaccone, G., Grande, G., Binetti, G., Papenberg, G., Hampel, H., Bailly, H., Zetterberg, H., Soininen, H., Karlsson, I.K., Alvarez, I., Appollonio, I., Giegling, I., Skoog, I., Saltvedt, I., Rainero, I., Rosas Allende, I., Hort, J., Diehl-Schmid, J., Van Dongen, J., Vidal, J-S, Lehtisalo, J., Wiltfang, J., Thomassen, J.Q., Kornhuber, J., Haines, J.L., Vogelgsang, J., Pineda, J.A., Fortea, J., Popp, J., Deckert, J., Buerger, K., Morgan, K., Fließbach, K., Sleegers, K., Molina-Porcel, L., Kilander, L., Weinhold, L., Farrer, L.A., Wang, L-S, Kleineidam, L., Farotti, L., Parnetti, L., Tremolizzo, L., Hausner, L., Benussi, L., Froelich, L., Ikram, M.A., Deniz-Naranjo, M.C., Tsolaki, M., Rosende-Roca, M., Löwenmark, M., Hulsman, M., Spallazzi, M., Pericak-Vance, M.A., Esiri, M., Bernal Sánchez-Arjona, M., Dalmasso, M.C., Martínez-Larrad, M.T., Arcaro, M., Nöthen, M.M., Fernández-Fuertes, M., Dichgans, M., Ingelsson, M., Herrmann, M.J., Scherer, M., Vyhnalek, M., Kosmidis, M.H., Yannakoulia, M., Schmid, M., Ewers, M., Heneka, M.T., Wagner, M., Scamosci, M., Kivipelto, M., Hiltunen, M., Zulaica, M., Alegret, M., Fornage, M., Roberto, N., van Schoor, N.M., Seidu, N.M., Banaj, N., Armstrong, N.J., Scarmeas, N., Scherbaum, N., Goldhardt, O., Hanon, O., Peters, O., Skrobot, O.A., Quenez, O., Lerch, O., Bossù, P., Caffarra, P., Dionigi Rossi, P., Sakka, P., Hoffmann, P., Holmans, P.A., Fischer, P., Riederer, P., Yang, Q., Marshall, R., Kalaria, R.N., Mayeux, R., Vandenberghe, R., Cecchetti, R., Ghidoni, R., Frikke-Schmidt, R., Sorbi, S., Hägg, S., Engelborghs, S., Helisalmi, S., Botne Sando, S., Kern, S., Archetti, S., Boschi, S., Fostinelli, S., Gil, S., Mendoza, S., Mead, S., Ciccone, S., Djurovic, S., Heilmann-Heimbach, S., Riedel-Heller, S., Kuulasmaa, T., del Ser, T., Lebouvier, T., Polak, T., Ngandu, T., Grimmer, T., Bessi, V., Escott-Price, V., Giedraitis, V., Deramecourt, V., Maier, W., Jian, X., Pijnenburg, Y.A.L., Smith, A.D., Saenz, A., Bizzarro, A., Lauria, A., Vacca, A., Solomon, A., Anastasiou, A., Richardson, A., Boland, A., Koivisto, A., Daniele, A., Greco, A., Marianthi, A., McGuinness, B., Fin, B., Ferrari, Ca., Custodero, C., Ferrarese, C., Ingino, C., Mangone, C., Reyes Toso, C., Martinez, C., Cuesta, C., Muchnik, C., Joachim, C., Ortiz, C., Besse, C., Johansson, C., Zoia, C.P., Laske, C., Anastasiou, C., Palacio, D.L., Politis, D.G., Janowitz, D., Craig, D., Mann, D.M., Neary, D., Jürgen, D., Daian, D., Belezhanska, D., Kohler, E., Castaño, E.M., Koutsouraki, E., Chipi, E., De Roeck, E., Costantini, E., Vardy, E.R.L.C., Piras, F., Roveta, F., Prestia, F.A., Assogna, F., Salani, F., Sala, G., Lacidogna, G., Novack, G., Wilcock, G., Thonberg, H., Kölsch, H., Weber, H., Boecker, H., Etchepareborda, I., Piaceri, I., Tuomilehto, J., Lindström, J., Laczo, J., Johnston, J., Deleuze, J-F, Harris, J., Schott, J.M., Priller, J., Bacha, J.I., Snowden, J., Lisso, J., Mihova, K.Y., Traykov, L., Morelli, L., Brusco, L.I., Rainer, M., Takalo, M., Bjerke, M., Del Zompo, M., Serpente, M., Sanchez Abalos, M., Rios, M., Peltonen, M., Herrman, M.J., Kohler, M., Rojo, M., Jones, M., Orsini, M., Medel, N., Olivar, N., Fox, N.C., Salvadori, N., Hooper, N.M., Galeano, P., Solis, P., Bastiani, P., Mecocci, P., Passmore, P., Heun, R., Antikainen, R., Olaso, R., Perneczky, R., Germani, S., López-García, S., Love, S., Mehrabian, S., Bagnoli, S., Kochen, S., Andreoni, S., Teipel, S., Todd, S., Pickering-Brown, S., Natunen, T., Tegos, T., Laatikainen, T., Strandberg, T., Polvikoski, T.M., Matoska, V., Ciullo, V., Cores, V., Solfrizzi, V., Lisetti, V., Sevillano, Z., Aguilera, N., Alarcon, E., Boada, M., Buendia, M., Cañabate, P., Carracedo, A., Diego, S., Gailhajenet, A., Guitart, M., González-Pérez, A., Ibarria, M., Lafuente, A., Macias, J., Maroñas, O., Martín, E., Martínez, M. T., Marquié, M., Mauleón, A., Moreno, M., Orellana, A., Pancho, A., Pelejá, E., Pérez-Cordon, A., Pineda, J. A., Preckler, S., Real, L. M., Ruiz, A., Sáez, M. E., Sanabria, A., Serrano-Rios, M., Tárraga, L., Vargas, L., Adarmes-Gómez, A. D., Alonso, M. D., Álvarez, I., Álvarez, V., Amer-Ferrer, G., Antequera, M., Bernal, M., Bullido, M.J., Burguera, J.A., Carrillo, F., Carrión-Claro, M., Casajeros, M.J., Clarimón, J., Cruz-Gamero, J.M., de Pancorbo, M.M., Escuela, R., Garrote-Espina, L., García-Alberca, J.M., Garcia Madrona, S., Garcia-Ribas, G., Gómez-Garre, P., Hevilla, S., Jesús, S., Labrador Espinosa, M.A., Legaz, A., Lleó, A., Lopez de Munain, A., Macias-García, D., Manzanares, S., Marín, M., Marín-Muñoz, J., Marín, T., Martínez, B., Martínez, C., Martínez, V., Martínez-Lage Álvarez, P., Medina, M., Mendioroz Iriarte, M., Mir, P., Molinuevo, J.L., Pastor, P., Pérez Tur, J., Periñán-Tocino, T., Pineda-Sanchez, R., Piñol-Ripoll, G., Real de Asúa, D., Rodrigo, S., Rodríguez-Rodríguez, E., Sanchez del Valle Díaz, R., Sánchez-Juan, P., Sastre, I., Vicente, M.P., Vigo-Ortega, R., Vivancos, L., Macleod, C., McCracken, C., Brayne, C., Bresner, C., Grozeva, D., Bellou, E., Sommerville, E.W., Matthews, F., Leonenko, G., Menzies, G., Windle, G., Harwood, J., Phillips, J., Bennett, K., Luckuck, L., Clare, L., Woods, R., Saad, S., Burholt, V., Kehoe, P.G., Pérez-Tur, J., Real, L.M., Scheltens, P., Holstege, H., Sáez, M.E., Carracedo, Á., Amouyel, P., Schellenberg, G.D., Williams, J., Seshadri, S., van Duijn, C.M., Mather, K.A., Sánchez-Valle, R., Serrano-Ríos, M., Blennow, K., Huisman, M., Andreassen, O.A., Posthuma, D., van der Flier, W.M., Ramirez, A., Lambert, J-C, van der Lee, S.J., de Rojas, I., Moreno-Grau, S., Tesi, N., Grenier-Boley, B., Andrade, V., Jansen, I.E., Pedersen, N.L., Stringa, N., Zettergren, A., Hernández, I., Montrreal, L., Antúnez, C., Antonell, A., Tankard, R.M., Bis, J.C., Sims, R., Bellenguez, C., Quintela, I., González-Perez, A., Calero, M., Franco-Macías, E., Macías, J., Blesa, R., Cervera-Carles, L., Menéndez-González, M., Frank-García, A., Royo, J.L., Moreno, F., Huerto Vilas, R., Baquero, M., Diez-Fairen, M., Lage, C., García-Madrona, S., García-González, P., Alarcón-Martín, E., Valero, S., Sotolongo-Grau, O., Ullgren, A., Naj, A.C., Lemstra, A.W., Benaque, A., Pérez-Cordón, A., Benussi, A., Rábano, A., Padovani, A., Squassina, A., de Mendonça, A., Arias Pastor, A., Kok, A.A.L., Meggy, A., Pastor, A.B., Espinosa, A., Corma-Gómez, A., Martín Montes, A., Sanabria, Á., DeStefano, A.L., Schneider, A., Haapasalo, A., Kinhult Ståhlbom, A., Tybjærg-Hansen, A., Hartmann, A.M., Spottke, A., Corbatón-Anchuelo, A., Rongve, A., Borroni, B., Arosio, B., Nacmias, B., Nordestgaard, B.G., Kunkle, B.W., Charbonnier, C., Abdelnour, C., Masullo, C., Martínez Rodríguez, C., Muñoz-Fernandez, C., Dufouil, C., Graff, C., Ferreira, C.B., Chillotti, C., Reynolds, C.A., Fenoglio, C., Van Broeckhoven, C., Clark, C., Pisanu, C., Satizabal, C.L., Holmes, C., Buiza-Rueda, D., Aarsland, D., Rujescu, D., Alcolea, D., Galimberti, D., Wallon, D., Seripa, D., Grünblatt, E., Dardiotis, E., Düzel, E., Scarpini, E., Conti, E., Rubino, E., Gelpi, E., Rodriguez-Rodriguez, E., Duron, E., Boerwinkle, E., Ferri, E., Tagliavini, F., Küçükali, F., Pasquier, F., Sanchez-Garcia, F., Mangialasche, F., Jessen, F., Nicolas, G., Selbæk, G., Ortega, G., Chêne, G., Hadjigeorgiou, G., Rossi, G, Spalletta, G., Giaccone, G., Grande, G., Binetti, G., Papenberg, G., Hampel, H., Bailly, H., Zetterberg, H., Soininen, H., Karlsson, I.K., Alvarez, I., Appollonio, I., Giegling, I., Skoog, I., Saltvedt, I., Rainero, I., Rosas Allende, I., Hort, J., Diehl-Schmid, J., Van Dongen, J., Vidal, J-S, Lehtisalo, J., Wiltfang, J., Thomassen, J.Q., Kornhuber, J., Haines, J.L., Vogelgsang, J., Pineda, J.A., Fortea, J., Popp, J., Deckert, J., Buerger, K., Morgan, K., Fließbach, K., Sleegers, K., Molina-Porcel, L., Kilander, L., Weinhold, L., Farrer, L.A., Wang, L-S, Kleineidam, L., Farotti, L., Parnetti, L., Tremolizzo, L., Hausner, L., Benussi, L., Froelich, L., Ikram, M.A., Deniz-Naranjo, M.C., Tsolaki, M., Rosende-Roca, M., Löwenmark, M., Hulsman, M., Spallazzi, M., Pericak-Vance, M.A., Esiri, M., Bernal Sánchez-Arjona, M., Dalmasso, M.C., Martínez-Larrad, M.T., Arcaro, M., Nöthen, M.M., Fernández-Fuertes, M., Dichgans, M., Ingelsson, M., Herrmann, M.J., Scherer, M., Vyhnalek, M., Kosmidis, M.H., Yannakoulia, M., Schmid, M., Ewers, M., Heneka, M.T., Wagner, M., Scamosci, M., Kivipelto, M., Hiltunen, M., Zulaica, M., Alegret, M., Fornage, M., Roberto, N., van Schoor, N.M., Seidu, N.M., Banaj, N., Armstrong, N.J., Scarmeas, N., Scherbaum, N., Goldhardt, O., Hanon, O., Peters, O., Skrobot, O.A., Quenez, O., Lerch, O., Bossù, P., Caffarra, P., Dionigi Rossi, P., Sakka, P., Hoffmann, P., Holmans, P.A., Fischer, P., Riederer, P., Yang, Q., Marshall, R., Kalaria, R.N., Mayeux, R., Vandenberghe, R., Cecchetti, R., Ghidoni, R., Frikke-Schmidt, R., Sorbi, S., Hägg, S., Engelborghs, S., Helisalmi, S., Botne Sando, S., Kern, S., Archetti, S., Boschi, S., Fostinelli, S., Gil, S., Mendoza, S., Mead, S., Ciccone, S., Djurovic, S., Heilmann-Heimbach, S., Riedel-Heller, S., Kuulasmaa, T., del Ser, T., Lebouvier, T., Polak, T., Ngandu, T., Grimmer, T., Bessi, V., Escott-Price, V., Giedraitis, V., Deramecourt, V., Maier, W., Jian, X., Pijnenburg, Y.A.L., Smith, A.D., Saenz, A., Bizzarro, A., Lauria, A., Vacca, A., Solomon, A., Anastasiou, A., Richardson, A., Boland, A., Koivisto, A., Daniele, A., Greco, A., Marianthi, A., McGuinness, B., Fin, B., Ferrari, Ca., Custodero, C., Ferrarese, C., Ingino, C., Mangone, C., Reyes Toso, C., Martinez, C., Cuesta, C., Muchnik, C., Joachim, C., Ortiz, C., Besse, C., Johansson, C., Zoia, C.P., Laske, C., Anastasiou, C., Palacio, D.L., Politis, D.G., Janowitz, D., Craig, D., Mann, D.M., Neary, D., Jürgen, D., Daian, D., Belezhanska, D., Kohler, E., Castaño, E.M., Koutsouraki, E., Chipi, E., De Roeck, E., Costantini, E., Vardy, E.R.L.C., Piras, F., Roveta, F., Prestia, F.A., Assogna, F., Salani, F., Sala, G., Lacidogna, G., Novack, G., Wilcock, G., Thonberg, H., Kölsch, H., Weber, H., Boecker, H., Etchepareborda, I., Piaceri, I., Tuomilehto, J., Lindström, J., Laczo, J., Johnston, J., Deleuze, J-F, Harris, J., Schott, J.M., Priller, J., Bacha, J.I., Snowden, J., Lisso, J., Mihova, K.Y., Traykov, L., Morelli, L., Brusco, L.I., Rainer, M., Takalo, M., Bjerke, M., Del Zompo, M., Serpente, M., Sanchez Abalos, M., Rios, M., Peltonen, M., Herrman, M.J., Kohler, M., Rojo, M., Jones, M., Orsini, M., Medel, N., Olivar, N., Fox, N.C., Salvadori, N., Hooper, N.M., Galeano, P., Solis, P., Bastiani, P., Mecocci, P., Passmore, P., Heun, R., Antikainen, R., Olaso, R., Perneczky, R., Germani, S., López-García, S., Love, S., Mehrabian, S., Bagnoli, S., Kochen, S., Andreoni, S., Teipel, S., Todd, S., Pickering-Brown, S., Natunen, T., Tegos, T., Laatikainen, T., Strandberg, T., Polvikoski, T.M., Matoska, V., Ciullo, V., Cores, V., Solfrizzi, V., Lisetti, V., Sevillano, Z., Aguilera, N., Alarcon, E., Boada, M., Buendia, M., Cañabate, P., Carracedo, A., Diego, S., Gailhajenet, A., Guitart, M., González-Pérez, A., Ibarria, M., Lafuente, A., Macias, J., Maroñas, O., Martín, E., Martínez, M. T., Marquié, M., Mauleón, A., Moreno, M., Orellana, A., Pancho, A., Pelejá, E., Pérez-Cordon, A., Pineda, J. A., Preckler, S., Real, L. M., Ruiz, A., Sáez, M. E., Sanabria, A., Serrano-Rios, M., Tárraga, L., Vargas, L., Adarmes-Gómez, A. D., Alonso, M. D., Álvarez, I., Álvarez, V., Amer-Ferrer, G., Antequera, M., Bernal, M., Bullido, M.J., Burguera, J.A., Carrillo, F., Carrión-Claro, M., Casajeros, M.J., Clarimón, J., Cruz-Gamero, J.M., de Pancorbo, M.M., Escuela, R., Garrote-Espina, L., García-Alberca, J.M., Garcia Madrona, S., Garcia-Ribas, G., Gómez-Garre, P., Hevilla, S., Jesús, S., Labrador Espinosa, M.A., Legaz, A., Lleó, A., Lopez de Munain, A., Macias-García, D., Manzanares, S., Marín, M., Marín-Muñoz, J., Marín, T., Martínez, B., Martínez, C., Martínez, V., Martínez-Lage Álvarez, P., Medina, M., Mendioroz Iriarte, M., Mir, P., Molinuevo, J.L., Pastor, P., Pérez Tur, J., Periñán-Tocino, T., Pineda-Sanchez, R., Piñol-Ripoll, G., Real de Asúa, D., Rodrigo, S., Rodríguez-Rodríguez, E., Sanchez del Valle Díaz, R., Sánchez-Juan, P., Sastre, I., Vicente, M.P., Vigo-Ortega, R., Vivancos, L., Macleod, C., McCracken, C., Brayne, C., Bresner, C., Grozeva, D., Bellou, E., Sommerville, E.W., Matthews, F., Leonenko, G., Menzies, G., Windle, G., Harwood, J., Phillips, J., Bennett, K., Luckuck, L., Clare, L., Woods, R., Saad, S., Burholt, V., Kehoe, P.G., Pérez-Tur, J., Real, L.M., Scheltens, P., Holstege, H., Sáez, M.E., Carracedo, Á., Amouyel, P., Schellenberg, G.D., Williams, J., Seshadri, S., van Duijn, C.M., Mather, K.A., Sánchez-Valle, R., Serrano-Ríos, M., Blennow, K., Huisman, M., Andreassen, O.A., Posthuma, D., van der Flier, W.M., Ramirez, A., Lambert, J-C, and van der Lee, S.J.
Abstract: Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.
Published: 2021

11. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

Author: de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E., Pedersen, Nancy L., Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M., Bis, Joshua C., Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Monica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C., Lemstra, Afina W., Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A. L., Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anaïs, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L., Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M., Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G., Kunkle, Brian W., Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B., Chillotti, Caterina, Reynolds, Chandra A., Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L., Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K., Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L., Vogelgsang, Jonathan, Pineda, Juan A., Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A., Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M. Arfan, Deniz-Naranjo, M. Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A., Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M., Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J., Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H., Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T., Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M., Seidu, Nazib M., Banaj, Nerisa, Armstrong, Nicola J., Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Hoffmann, Per, Holmans, Peter A., Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N., Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A. L., Kehoe, Patrick Gavin, García-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J., Álvarez, Victoria, Lleó, Alberto, Real, Luis M., Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D., Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M., Mather, Karen A., Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A., Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M., Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J., Ruiz, Agustín, Universitat Autònoma de Barcelona, de Rojas, Itziar, Moreno-Grau, Sonia, Tesi, Niccolo, Grenier-Boley, Benjamin, Andrade, Victor, Jansen, Iris E., Pedersen, Nancy L., Stringa, Najada, Zettergren, Anna, Hernández, Isabel, Montrreal, Laura, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M., Bis, Joshua C., Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Franco-Macías, Emilio, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Frank-García, Ana, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Monica, Lage, Carmen, García-Madrona, Sebastián, García-González, Pablo, Alarcón-Martín, Emilio, Valero, Sergi, Sotolongo-Grau, Oscar, Ullgren, Abbe, Naj, Adam C., Lemstra, Afina W., Benaque, Alba, Pérez-Cordón, Alba, Benussi, Alberto, Rábano, Alberto, Padovani, Alessandro, Squassina, Alessio, de Mendonça, Alexandre, Arias Pastor, Alfonso, Kok, Almar A. L., Meggy, Alun, Pastor, Ana Belén, Espinosa, Ana, Corma-Gómez, Anaïs, Martín Montes, Angel, Sanabria, Ángela, DeStefano, Anita L., Schneider, Anja, Haapasalo, Annakaisa, Kinhult Ståhlbom, Anne, Tybjærg-Hansen, Anne, Hartmann, Annette M., Spottke, Annika, Corbatón-Anchuelo, Arturo, Rongve, Arvid, Borroni, Barbara, Arosio, Beatrice, Nacmias, Benedetta, Nordestgaard, Børge G., Kunkle, Brian W., Charbonnier, Camille, Abdelnour, Carla, Masullo, Carlo, Martínez Rodríguez, Carmen, Muñoz-Fernandez, Carmen, Dufouil, Carole, Graff, Caroline, Ferreira, Catarina B., Chillotti, Caterina, Reynolds, Chandra A., Fenoglio, Chiara, Van Broeckhoven, Christine, Clark, Christopher, Pisanu, Claudia, Satizabal, Claudia L., Holmes, Clive, Buiza-Rueda, Dolores, Aarsland, Dag, Rujescu, Dan, Alcolea, Daniel, Galimberti, Daniela, Wallon, David, Seripa, Davide, Grünblatt, Edna, Dardiotis, Efthimios, Düzel, Emrah, Scarpini, Elio, Conti, Elisa, Rubino, Elisa, Gelpi, Ellen, Rodriguez-Rodriguez, Eloy, Duron, Emmanuelle, Boerwinkle, Eric, Ferri, Evelyn, Tagliavini, Fabrizio, Küçükali, Fahri, Pasquier, Florence, Sanchez-Garcia, Florentino, Mangialasche, Francesca, Jessen, Frank, Nicolas, Gaël, Selbæk, Geir, Ortega, Gemma, Chêne, Geneviève, Hadjigeorgiou, Georgios, Rossi, Giacomina, Spalletta, Gianfranco, Giaccone, Giorgio, Grande, Giulia, Binetti, Giuliano, Papenberg, Goran, Hampel, Harald, Bailly, Henri, Zetterberg, Henrik, Soininen, Hilkka, Karlsson, Ida K., Alvarez, Ignacio, Appollonio, Ildebrando, Giegling, Ina, Skoog, Ingmar, Saltvedt, Ingvild, Rainero, Innocenzo, Rosas Allende, Irene, Hort, Jakub, Diehl-Schmid, Janine, Van Dongen, Jasper, Vidal, Jean-Sebastien, Lehtisalo, Jenni, Wiltfang, Jens, Thomassen, Jesper Qvist, Kornhuber, Johannes, Haines, Jonathan L., Vogelgsang, Jonathan, Pineda, Juan A., Fortea, Juan, Popp, Julius, Deckert, Jürgen, Buerger, Katharina, Morgan, Kevin, Fließbach, Klaus, Sleegers, Kristel, Molina-Porcel, Laura, Kilander, Lena, Weinhold, Leonie, Farrer, Lindsay A., Wang, Li-San, Kleineidam, Luca, Farotti, Lucia, Parnetti, Lucilla, Tremolizzo, Lucio, Hausner, Lucrezia, Benussi, Luisa, Froelich, Lutz, Ikram, M. Arfan, Deniz-Naranjo, M. Candida, Tsolaki, Magda, Rosende-Roca, Maitée, Löwenmark, Malin, Hulsman, Marc, Spallazzi, Marco, Pericak-Vance, Margaret A., Esiri, Margaret, Bernal Sánchez-Arjona, María, Dalmasso, Maria Carolina, Martínez-Larrad, María Teresa, Arcaro, Marina, Nöthen, Markus M., Fernández-Fuertes, Marta, Dichgans, Martin, Ingelsson, Martin, Herrmann, Martin J., Scherer, Martin, Vyhnalek, Martin, Kosmidis, Mary H., Yannakoulia, Mary, Schmid, Matthias, Ewers, Michael, Heneka, Michael T., Wagner, Michael, Scamosci, Michela, Kivipelto, Miia, Hiltunen, Mikko, Zulaica, Miren, Alegret, Montserrat, Fornage, Myriam, Roberto, Natalia, van Schoor, Natasja M., Seidu, Nazib M., Banaj, Nerisa, Armstrong, Nicola J., Scarmeas, Nikolaos, Scherbaum, Norbert, Goldhardt, Oliver, Hanon, Oliver, Peters, Oliver, Skrobot, Olivia Anna, Quenez, Olivier, Lerch, Ondrej, Bossù, Paola, Caffarra, Paolo, Dionigi Rossi, Paolo, Sakka, Paraskevi, Hoffmann, Per, Holmans, Peter A., Fischer, Peter, Riederer, Peter, Yang, Qiong, Marshall, Rachel, Kalaria, Rajesh N., Mayeux, Richard, Vandenberghe, Rik, Cecchetti, Roberta, Ghidoni, Roberta, Frikke-Schmidt, Ruth, Sorbi, Sandro, Hägg, Sara, Engelborghs, Sebastiaan, Helisalmi, Seppo, Botne Sando, Sigrid, Kern, Silke, Archetti, Silvana, Boschi, Silvia, Fostinelli, Silvia, Gil, Silvia, Mendoza, Silvia, Mead, Simon, Ciccone, Simona, Djurovic, Srdjan, Heilmann-Heimbach, Stefanie, Riedel-Heller, Steffi, Kuulasmaa, Teemu, del Ser, Teodoro, Lebouvier, Thibaud, Polak, Thomas, Ngandu, Tiia, Grimmer, Timo, Bessi, Valentina, Escott-Price, Valentina, Giedraitis, Vilmantas, Deramecourt, Vincent, Maier, Wolfgang, Jian, Xueqiu, Pijnenburg, Yolande A. L., Kehoe, Patrick Gavin, García-Ribas, Guillermo, Sánchez-Juan, Pascual, Pastor, Pau, Pérez-Tur, Jordi, Piñol-Ripoll, Gerard, Lopez de Munain, Adolfo, García-Alberca, Jose María, Bullido, María J., Álvarez, Victoria, Lleó, Alberto, Real, Luis M., Mir, Pablo, Medina, Miguel, Scheltens, Philip, Holstege, Henne, Marquié, Marta, Sáez, María Eugenia, Carracedo, Ángel, Amouyel, Philippe, Schellenberg, Gerard D., Williams, Julie, Seshadri, Sudha, van Duijn, Cornelia M., Mather, Karen A., Sánchez-Valle, Raquel, Serrano-Ríos, Manuel, Orellana, Adelina, Tárraga, Lluís, Blennow, Kaj, Huisman, Martijn, Andreassen, Ole A., Posthuma, Danielle, Clarimón, Jordi, Boada, Mercè, van der Flier, Wiesje M., Ramirez, Alfredo, Lambert, Jean-Charles, van der Lee, Sven J., Ruiz, Agustín, and Universitat Autònoma de Barcelona
Abstract: Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease. Known genetic loci account for only a fraction of the genetic contribution to Alzheimer's disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer's disease polygenic risk score.
Published: 2021

12. The Effects of Gene Mutations on Default Mode Network in Familial Alzheimer’s Disease

Author: Ove Almkvist, Anne Kinhult Ståhlbom, Lars-Olof Wahlund, Caroline Graff, Xiaozhen Li, Steinunn Thordardottir, Eric Westman, and Kaj Blennow
Subjects: Adult, Male, 0301 basic medicine, Amyloid, Models, Neurological, Tau protein, tau Proteins, Neuropsychological Tests, Gene mutation, behavioral disciplines and activities, Functional Laterality, Amyloid beta-Protein Precursor, 03 medical and health sciences, Apolipoproteins E, 0302 clinical medicine, Cerebrospinal fluid, Neuroimaging, Alzheimer Disease, Neural Pathways, mental disorders, Image Processing, Computer-Assisted, Presenilin-1, medicine, Humans, Dementia, Default mode network, Family Health, Amyloid beta-Peptides, Resting state fMRI, biology, General Neuroscience, Brain, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Peptide Fragments, humanities, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Mutation, biology.protein, Female, Geriatrics and Gerontology, Neuroscience, 030217 neurology & neurosurgery
Abstract: Familial Alzheimer's disease (FAD) mutations have very high penetrance but age at onset and rate of disease progression differ. Neuroimaging and cerebrospinal fluid (CSF) examinations in mutation carriers (MCs) may provide an opportunity to identify early biomarkers that can be used to track disease progression from presymptomatic to the dementia stages of disease. The default mode network (DMN) is a resting state neuronal network composed of regions known to associate with amyloid deposition in AD. We hypothesized that functional connectivity in the DMN might change at pre-clinical stages in FAD MCs and correlate with changes in CSF biomarkers as a consequence of AD brain pathology. To test the hypothesis, we compared the functional connectivity in DMN between pre-MCs/MCs and non-carriers (NCs). No significant differences between pre-MCs and NCs were observed. When comparing all MCs with NCs, significant decreased functional connectivity in the right inferior parietal lobule, right precuneus, and left posterior cingulate cortex were found. We also found statistically significant correlations between CSF amyloid-β 42 and tau protein levels and average Z-score, a resting-state functional MRI measurement reflecting the degree of the correlation between a given voxel's time courses and the time courses corresponding to DMN, from the region with statistical difference. The observed disruption of DMN and pathological levels of AD CSF-biomarkers in FAD MCs are similar to the changes described in sporadic AD, which give further support that amyloid and tau pathology impairs neuronal and synaptic function.
Published: 2017
Full Text: View/download PDF

13. Additional file 3: of Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study

Author: Thordardottir, Steinunn, Rodriguez-Vieitez, Elena, Almkvist, Ove, Ferreira, Daniel, Saint-Aubert, Laure, Kinhult-Ståhlbom, Anne, Thonberg, Håkan, Schöll, Michael, Westman, Eric, Wall, Anders, Eriksdotter, Maria, Zetterberg, Henrik, Blennow, Kaj, Nordberg, Agneta, and Graff, Caroline
Subjects: nervous system
Abstract: Longitudinal FDG and PiB-PET uptake in SUVr(/pons and/cerebellar gray matter) units in brothers A and B compared with the control group of noncarriers in representative ROIs. GM Gray matter, PCC Posterior cingulate cortex, SUVr Standardized uptake value ratio, Temp Temporal. (PDF 125 kb)
Published: 2018
Full Text: View/download PDF

14. Additional file 1: of Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study

Author: Thordardottir, Steinunn, Rodriguez-Vieitez, Elena, Almkvist, Ove, Ferreira, Daniel, Saint-Aubert, Laure, Kinhult-Ståhlbom, Anne, Thonberg, Håkan, Schöll, Michael, Westman, Eric, Wall, Anders, Eriksdotter, Maria, Zetterberg, Henrik, Blennow, Kaj, Nordberg, Agneta, and Graff, Caroline
Abstract: Longitudinal z-scores for the RAVL total learning test measuring episodic memory in brothers A and B. The scatterplot shows episodic memory as evaluated by the RAVL total learning test and expressed in z-score values versus years to the expected clinical onset of Alzheimer’s disease. The longitudinal trajectories are illustrated by LOESS curves for brothers A and B. RAVL Rey Auditory Verbal Learning. (PDF 222 kb)
Published: 2018
Full Text: View/download PDF

15. Additional file 2: of Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study

Author: Thordardottir, Steinunn, Rodriguez-Vieitez, Elena, Almkvist, Ove, Ferreira, Daniel, Saint-Aubert, Laure, Kinhult-Ståhlbom, Anne, Thonberg, Håkan, Schöll, Michael, Westman, Eric, Wall, Anders, Eriksdotter, Maria, Zetterberg, Henrik, Blennow, Kaj, Nordberg, Agneta, and Graff, Caroline
Abstract: Longitudinal FDG and PiB PET scans for brothers A and B, and corresponding uptake values in SUVr(/cerebellar gray matter) and z-scores. The two upper rows of the figure represent the longitudinal FDG and PiB PET scans for brother A during repeated follow-up examinations. The year of each examination is noted at the top of each column. The lower two rows of the figure represent the corresponding longitudinal FDG and PiB PET scans for brother B. The values included in the tables are standardized uptake value ratios (SUVr) for the ROIs in the study, with the cerebellar gray matter used as a reference region, as well as the corresponding z-score values with respect to the control group of noncarriers. FDG z-score values less than − 1.96 and PiB z-score values greater than + 1.96 are indicated in bold italic type. FDG [18F]fluorodeoxyglucose, GM Gray matter, PiB [11C]Pittsburgh compound B, SUVr Standardized uptake value ratio. (PDF 1471 kb)
Published: 2018
Full Text: View/download PDF

16. Prospective blinded surveillance screening of Swedish women with increased hereditary risk of breast cancer

Author: Anna von Wachenfeldt, Dieter Ulitzsch, Gunilla Svane, Annelie Liljegren, Helene Grundström, Ann Sundbom, Anne Kinhult Ståhlbom, Sandra Eloranta, Per Sundén, Edward Azavedo, and Brita Arver
Subjects: Adult, Cancer Research, medicine.medical_specialty, Heterozygote, Population, Breast Neoplasms, Prevention program, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Ultrasound, medicine, Mammography, Humans, Mass Screening, Genetic Predisposition to Disease, 030212 general & internal medicine, Medical diagnosis, Family history, education, Mass screening, Early Detection of Cancer, Aged, Hereditary breast cancer, BRCA2 Protein, Sweden, education.field_of_study, Surveillance, medicine.diagnostic_test, Obstetrics, business.industry, BRCA1 Protein, Middle Aged, medicine.disease, BRCA1, Magnetic Resonance Imaging, Clinical Trial, BRCA2, Oncology, 030220 oncology & carcinogenesis, Mutation, Lifetime risk, Female, business, Cohort study
Abstract: Purpose To evaluate the sensitivity and specificity of different screening modalities in women with a family history of breast cancer. Methods Our blinded, prospective, comparative cohort analysis included three types of screening, mammography, ultrasound, and clinical breast examination once per year for 6 years. Eligible patients for this study were healthy women with ≥ 17% lifetime risk of breast cancer or with a mutation in BRCA1 or BRCA2. Results A total of 632 women were screened between 2002 and 2012 (each for 6 years). During the study, 30 women were diagnosed with breast cancer, with 10 of these diagnoses occurring between screening visits, and six of the 10 diagnosed women were gene carriers. The clinical presentation for the women diagnosed with breast cancer was followed until 2017. No consistent patterns for the diagnostic capacity of the different screening modalities were found, although mammography showed low sensitivity, whereas ultrasound showed better sensitivity in three of the six rounds. The specificity was high in mammography and improved in ultrasound over time. Most importantly, clinical breast examination provided no additional information toward the diagnosis of breast cancer. Conclusion Neither mammography nor ultrasound performed yearly were sensitive enough as standalone modalities, although high specificity was confirmed. Our findings indicate that high risk (> 29% life time risk) individuals and gene carriers can be screened biannually, using the same protocol as used in mutation carriers. Our results also suggest that low-risk groups (
Published: 2017

17. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Author: John Hardy, Nick C. Fox, Lena Lilius, Christine Van Broeckhoven, Mindy J. Katz, Carlos Cruchaga, Joshua W. Miller, Carol Brayne, Letizia Concari, Christopher Shaw, Minerva M. Carrasquillo, Richard Mayeux, Anne Boland, Charles DeCarli, Helena C. Chui, Laura B. Cantwell, Yoland Aladro Benito, Chuang Kuo Wu, Elaine R. Peskind, Andrew McDavid, M. Ilyas Kamboh, Amanda Smith, Pascual Sánchez-Juan, Jean-François Deleuze, Jayanadra J. Himali, Thomas H. Mosley, Thomas J. Montine, Chuanhai Cao, Andreas J. Forstner, Thomas G. Beach, Robert Barber, Miquel Aguilar, Liming Qu, Jerome I. Rotter, Matthew J. Huentelman, Christiane Reitz, Christopher J. O'Donnell, Steven G. Younkin, Bradley T. Hyman, Bruce L. Miller, Rachelle S. Doody, Eric B. Larson, Ronald L. Hamilton, Todd E. Golde, Steven E. Arnold, Melissa E. Garcia, Rachel Raybould, Lena Kilander, Mark A. Sager, Kevin Morgan, Kathryn L. Lunetta, William Perry, Joseph D. Buxbaum, Craig S. Atwood, Thomas D. Bird, Michael Conlon O'Donovan, Robert Olaso, Juan Fortea, Susanne Moebus, Lisa L. Barnes, Rachel Marshall, Huntington Potter, Mercè Boada, Shahzad Ahmad, Paolo Caffarra, Daniel C. Marson, Jonathan L. Haines, Perrie M. Adams, John M Olichney, Lars Lannfelt, Stefanie Heilmann-Heimbach, Markus M. Nöthen, Shubhabrata Mukherjee, John Malamon, Xue Wang, Christopher S. Carlson, Karen Ritchie, Roger N. Rosenberg, Paul K. Crane, Alexa S. Beiser, Céline Bellenguez, Robert C. Green, Maria Urbano, Petra Proitsi, John Powell, Elisa Majounie, Ammar Al-Chalabi, Hakon Hakonarson, Yogen Patel, Martin Scherer, Julie Williams, Richard B. Lipton, Vincent Dermecourt, Adam L. Boxer, Gerard D. Schellenberg, David G. Clark, Anita L. DeStefano, Joel H. Kramer, Victoria Alvarez, Nandini Badarinarayan, Oscar L. Lopez, Chris Corcoran, Ubaldo Bonuccelli, Donald R. Royall, James Bowen, Monica Diez Fairen, Tricia A. Thornton-Wells, Nilufer Ertekin-Taner, Florence Pasquier, Martin Ingelsson, Yi Zhao, John R. Gilbert, Valentina Escott-Price, Amanda B. Kuzma, Fabienne Garzia, Reinhard Heun, Otto Valladares, Andrew J. Saykin, Sara Ortega-Cubero, Liana G. Apostolova, Henry L. Paulson, John K Kauwe, Imelda Barber, Carolina Ceballos Diaz, Douglas Galasko, M. Arfan Ikram, Lluís Tárraga, Carlo Caltagirone, Joan S. Reisch, Wolfgang Maier, Bruno Vellas, Rebecca Sims, Angela Hodges, Matthew P. Frosch, Isabel Henández, Annakaisa Haapasalo, Thor Aspelund, Håkan Thonberg, Aimee Pierce, Roger L. Albin, Wayne W. Poon, Rebecca Sussams, Amy Braddel, Ranjan Duara, Albert V. Smith, Kirk C. Wilhelmsen, Gianfranco Spalletta, Simon Lovestone, Peter Passmore, Ana Frank-García, Cynthia M. Carlsson, Jade Chapman, Nathan D. Price, Philip L. De Jager, John M. Ringman, Seung Hoan Choi, Nicola Denning, Michael John Owen, Clinton T. Baldwin, Amalia C. Bruni, Denis A. Evans, Rudolph E. Tanzi, Dominique Campion, Laura Fratiglioni, Alberto Lleó, Per Hoffmann, Carole Dufouil, Charlotte Forsell, Alun Meggy, Charlene Thomas, Robert S. Stern, James B. Leverenz, Tatiana Foroud, William W. Seeley, James J. Lah, Brian A. Lawlor, Kenneth B. Fallon, Matthias Riemenschneider, Ryan M. Huebinger, Regina M. Carney, Clinton B. Wright, Didier Hannequin, Deborah Blacker, Anne Kinhult-Ståhlbom, Ekaterina Rogaeva, Andrew P. Lieberman, Bernardino Ghetti, Linda J. Van Eldik, Bernadette McGuinness, Thomas Fairchild, Margaret A. Pericak-Vance, Ashok Raj, Reinhold Schmidt, Ronald C. Petersen, Harald Hampel, María J. Bullido, Steven L. Carroll, Maria Candida Deniz Naranjo, Kathleen A. Welsh-Bohmer, Myriam Fornage, Joseph F. Quinn, Caroline Graff, Claudia L. Satizabal, Patrice L. Whitehead, David Wallon, Christopher Medway, Lindsay A. Farrer, Vilmundur Gudnason, Peter St George-Hyslop, Pau Pastor, Frank Jessen, Erin L. Abner, Johanna Jakobsdottir, Hieab H.H. Adams, Roberta Cecchetti, Walter A. Kukull, Thomas S. Wingo, Michelle K. Lupton, Valur Emilsson, Susan M. McCurry, Simon Mead, Hilkka Soininen, Sandra Weintraub, Amy Gerrish, Lindy E. Harrell, Lina Keller, Jean-Charles Lambert, Denise Harold, Stephen Todd, Wei Gu, Maura Gallo, Najaf Amin, Lenore J. Launer, Eleonora Sacchinelli, Mikko Hiltunen, Cécile Dulary, Eliecer Coto, Xueqiu Jian, Nathalie Fievet, Patrizia Mecocci, Sarah Taylor, Eric Boerwinkle, Maria Serpente, Ronald G. Munger, Ina Giegling, Carlo Masullo, Aoibhinn Lynch, Eliezer Masliah, Anne M. Koivisto, Chang En Yu, Qiong Yang, Benedetta Nacmias, Wayne C. McCormick, Kristelle Brown, Alessio Squassina, Deborah C. Mash, Brian W. Kunkle, Makrina Daniilidou, Alison Goate, David Carrell, Kara L. Hamilton-Nelson, Sandra Barral, Vincent Chouraki, Kristel Sleegers, Frank J. Wolters, Joseph E. Parisi, Iwona Kłoszewska, Ronald C. Kim, Sonia Moreno-Grau, Marina Arcaro, Carmen Muñoz Fernadez, Vernon S. Pankratz, Duane Beekly, Sabrina Pichler, Gislain Septier, Delphine Bacq, Amanda J. Myers, Adam C. Naj, Frank Martiniuk, Sudha Seshadri, Badri N. Vardarajan, Joshua A. Sonnen, M.-Marsel Mesulam, Howard J. Rosen, James T. Becker, Chiara Fenoglio, Ge Li, Alberto Pilotto, Mary Sano, Olivier Hanon, Honghuang Lin, Jean Paul G. Vonsattel, W. T. Longstreth, Daniela Galimberti, David C. Rubinsztein, RoseMarie Brundin, Vilmantas Giedraitis, Christine M. Hulette, Peter Holmans, Martin Dichgans, Maria Vronskaya, Céline Derbois, Michelangelo Mancuso, Constantine G. Lyketsos, Christophe Tzourio, Jacques Epelbaum, Raffaele Maletta, Mariet Allen, Hong-Dong Li, James R. Burke, Rik Vandenberghe, David G. Mann, Bruce M. Psaty, Lawrence S. Honig, Beth A. Dombroski, Erik D. Roberson, Cornelia M. van Duijn, Benjamin Grenier-Boley, Seppo Helisalmi, Jean-François Dartigues, Russell H. Swerdlow, Paola Bossù, Ashley R. Winslow, Elio Scarpini, Lesley Jones, Sebastien Engelborghs, John Q. Trojanowski, Jeffrey Kaye, Jenny Lord, Chiara Cupidi, Janet A. Johnston, Dan Rujescu, Feroze Golamaully, Anne Braae, Rafael Blesa, L. Adrienne Cupples, Dennis W. Dickson, Gail P. Jarvik, David W. Fardo, David H. Cribbs, Michael Gill, Jose Bras, Allan I. Levey, Jennifer Williamson, Rhodri Thomas, John C. Morris, Lei Yu, Debby W. Tsuang, Annette M. Hartmann, John H. Growdon, John Collinge, Claudine Berr, Fernando Rivadeneira, Oliver Peters, Albert Hofman, Frank M. LaFerla, Vivianna M. Van Deerlin, James Uphill, David A. Bennett, Onofre Combarros, Gudny Eiriksdottir, Jeremy D. Burgess, Melanie L. Dunstan, Elizabeth Crocco, Keeley J. Brookes, Robert R. Graham, Lon S. Schneider, Eden R. Martin, Matt Hill, Neill R. Graff-Radford, Joseph T. Hughes, Vincenzo Solfrizzi, Taniesha Morgan, Antonio Ciaramella, Bruno Dubois, Juan C. Troncoso, Paolo Bosco, Jordi Clarimón, Daniel H. Geschwind, Virginia Boccardi, Barry Reisberg, Timothy W. Behrens, Annette L. Fitzpatrick, Salvatore Spina, Alexis Brice, Eileen H. Bigio, Marla Gearing, Jeffrey M. Burns, Carol A. Miller, Marilyn S. Albert, Sven J. van der Lee, Sandro Sorbi, C. Dirk Keene, Daniel Levy, Antonio Daniele, Eric M. Reiman, Paramita Chakrabarty, Oscar Sotolongo-Grau, Helena Schmidt, Francesco Panza, Murray A. Raskind, Rita Guerreiro, Gyungah Jun, Anna Karydas, Markus Leber, Harry V. Vinters, Cory C. Funk, Charles C. White, Jill R. Murrell, Sid E. O'Bryant, Nigel J. Cairns, Josée Dupuis, Ann C. McKee, Julie A. Schneider, Megan L. Grove, Malcolm B. Dick, Bradley F. Boeve, Jennifer A. Brody, Sanjay Asthana, Agustín Ruiz, Stefan Herms, Yuning Chen, David Craig, Neil W. Kowall, Maria Donata Orfei, JoAnn T. Tschanz, Florentino Sanchez Garcia, Manuel Mayhaus, Alfredo Ramirez, James Turton, André G. Uitterlinden, Davide Seripa, Lee-Way Jin, Kelley Faber, Maria C. Norton, Shuo Li, Steven H. Ferris, Steffi G. Riedel-Heller, Joshua C. Bis, Li-San Wang, Johannes Kornhuber, Peter Paul De Deyn, Martin R. Farlow, Randall L. Woltjer, Gary W. Beecham, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Icelandic Heart Association [Kopavogur, Iceland] (IHA), John P. Hussman Institute for Human Genomics [Miami, FL, USA], University of Miami [Coral Gables], Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Medicine, University of Washington [Seattle], Dr. John T. Macdonald Foundation [Miami, FL, USA] (Department of Human Genetics), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], Department of Molecular Genetics, Institut Català de Neurociències Aplicades [Barcelona, Spain], Well Advanced Solutions, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], The University of Texas Health Science Center at Houston (UTHealth), Columbia University [New York], University of Eastern Finland, Life & Brain Center - Department of Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), John P. Hussman Institute for Human Genomics, Neurobiologie de la Croissance et de la Senescence, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Emmy Noether Project (SFB 833), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Boston University [Boston] (BU), Department of Genomics, Institute for Systems Biology [Seattle, WA, USA], Universitätsklinikum Bonn (UKB), Centre of Excellence for Robotic Vision [Canberra], Australian Research Council [Canberra] (ARC), Neuroscience and Mental Health Research Institute [Cardiff, UK] (School of Medicine), Boston University School of Medicine (BUSM), Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, University of Pennsylvania [Philadelphia], Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Department of Epidemiology and Biostatistics, ERASMUS, Hospital Universitario Doctor Negrín [Las Palmas de Gran Canaria, Spain], Department of Neurodegenerative Diseases, University of Mississippi Medical Center (UMMC), Pathology and Laboratory Medicine [Philadelphia, PA, USA] (Penn Neurodegeneration Genomics Center), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioinformatics, GlaxoSmithKline, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], University of Nottingham, UK (UON), University of Texas Health Science Center, Department of Neurobiology, Caring Sciences and Society (NVS), University of Bari Aldo Moro (UNIBA), Ageing Group, Centre for Public Health, Queen's University [Belfast] (QUB), Mayo Clinic [Jacksonville], Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Università degli Studi di Perugia (UNIPG), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), CHU Rouen, Normandie Université (NU), Universidad Autonoma de Madrid (UAM), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Florida [Gainesville] (UF), University of Parma = Università degli studi di Parma [Parme, Italie], Center for Cognitive Disorders AUSL [Parma, Italy], School of Public Health [Boston], Uppsala University, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Xi'an Jiaotong University (Xjtu), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Institute of Gerontology and Geriatrics, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Geriatric Medicine and Metabolic Diseases, Departments of Nuclear Medicine, University Medical Centre Hamburg-Eppendorf [Hamburg, Germany], University of Texas Southwestern Medical Center [Dallas], University of Cologne, Laboratoire d'Etudes et de Recherche en Informatique d'Angers (LERIA), Université d'Angers (UA), Johns Hopkins University (JHU), Universität Leipzig [Leipzig], University of Iceland [Reykjavik], Metacohorts Consortium, Harvard School of Public Health, Catholic University of Rome, Medical University Graz, Baylor College of Medicine (BCM), Baylor University, University of North Texas Health Science Center [Fort Worth], Santa Lucia Foundation (IRCCS), Nextel S.A. [Bilbao], Massachusetts General Hospital [Boston], Department of Pathology and Laboratory Medicine and Indiana Alzheimer disease Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Joint Institute for the Study of the Atmosphere and Ocean (JISAO), Beijing University of Technology, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Saul B. Korey Department of Neurology, Albert Einstein College of Medicine [New York]-Yeshiva University, Utah State University (USU), Fundació per la Recerca Biomèdica i Social Mútua Terrassa [Barcelona, Spain], Hospital Universitario Mutua de Terrassa, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Medical University of Łódź (MUL), University of Leicester, MRC Prion Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Fondazione Istituto di Ricerca e Cura Carattere Scientifico [Rome], Università degli Studi di Roma Tor Vergata [Roma], Saarland University Hospital, Universitat Autònoma de Barcelona (UAB), Regional Neurogenetic Centre [Lamezia Terme, Italy] (CRN - ASP Catanzaro), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Universidade do Porto, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Experimental and Clinical Pharmacology, St. James Hospital and Trinity College [Dublin, Ireland], School of Medicine [Dublin], Trinity College Dublin, University of Sheffield [Sheffield], Lancaster University, University of Michigan [Ann Arbor], University of Michigan System, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, University of Wisconsin-Madison, Rush Alzheimer Disease Center [Chicago, IL, États-Unis], Rush University Medical Center [Chicago], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), School of Engineering [Cardiff], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Northwestern University Feinberg School of Medicine, Mayo Clinic [Rochester], Swedish Medical Center [Seattle, WA, USA], University of California [San Francisco] (UCSF), University of California, Duke University [Durham], University of Kansas Medical Center [Lawrence], Laboratory of Molecular Neuropsychiatry, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Washington University in Saint Louis (WUSTL), University of South Florida [Tampa] (USF), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Medical University of South Carolina [Charleston] (MUSC), University of Southern California (USC), Los Alamos National Laboratory (LANL), Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neurology Department, University of California, Davis (UCDavis-Neuro), University of California [Davis] (UC Davis), University of California [Irvine] (UCI), Mount Sinai Medical Center, Indiana State University, University of Alabama at Birmingham [ Birmingham] (UAB), University of Kentucky, New York University [New York] (NYU), NYU System (NYU), Department of Medical and Molecular Genetics, Department of Epidemiology and biostatistics, VU University Medical Center [Amsterdam], Emory University [Atlanta, GA], Department of Neurology, University of California-University of California-David Geffen School of Medicine [Los Angeles], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Department of Medical Genetics, HMNC Brain Health, Alzheimer Disease Research Laboratory, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Laboratoire d'Informatique, Systèmes, Traitement de l'Information et de la Connaissance (LISTIC), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Psychiatry, School of Medicine-Johns Hopkins University and Johns Hopkins Bayview Medical Center, Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Department of neurosciences, University of California [San Diego] (UC San Diego), Department of Physics and Astronomy [Fort Worth], Texas Christian University (TCU), Department of Computer Science [University of California, Davis], Indiana University System, Institute for Aging and Alzheimer’s Disease Research [Fort Worth] (IAADR), Department of Laboratory Medicine and Pathology, Mayo Clinic, Institute for Memory Impairments and Neurological Disorders [Irvine], University of Colorado Anschutz [Aurora], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Keck School of Medicine [Los Angeles], Indiana University [South Bend], Massachusetts General Hospital, Novartis Institutes for Biomedical Research [Cambridge, MA, USA], Departments of Pathology and Laboratory Medicine (Neuropathology) and Neurology, UCLA Medical Center-David Geffen School of Medicine [Los Angeles], University of California-University of California-University of California [Los Angeles] (UCLA), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Institut de Génomique d'Evry (IG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Antwerp (UA), Institute Born-Bunge, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], University of Kuopio, Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Laboratoire d'Analyse Génomique, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Inserm-U1167, Dpt Gériatrie [CHU Broca], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Epidemiology, University of Washington, School of Medicine [Los Angeles], Albert Einstein College of Medicine [New York], IdiPAZ - Instituto de Investigación La Paz [Madrid, Spain], Instituto de Física Teórica UAM/CSIC (IFT), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Department of Internal Medicine, University of Central Asturias [Oviedo, Spain], Human Genome Sequencing Center, Baylor College of Medicine, Baylor University-Baylor University, Department of Epidemiology, Erasmus Medical Centre, Translational Genomics Research Institute [Phoenix, AZ, USA], University of Arizona, Banner Alzheimer's Institute [Phoenix, AZ, États-Unis], University of Texas Health Science Center at San Antonio [San Antonio], Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department. of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Centre for Research in Neurodegenerative Diseases, VA Puget Sound Health Care System/GRECC [Seattle, WA, USA], University of Pisa - Università di Pisa, Pfizer Worldwide Research and Development [Cambridge, MA, USA], Università cattolica del Sacro Cuore [Piacenza e Cremona] (Unicatt), Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Saarland University [Saarbrücken], University of Bonn, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Cambridge Institute for Medical Research (CIMR), Department of Molecular Neurosciences, Institute of Neurology, UCL, Institute of Psychiatry, Institute of psychiatry, University of British Columbia (UBC), the Clinical Neuroscience Research Group, University of Manchester [Manchester]-Greater Manchester Neurosciences Centre, Aristotle University of Thessaloniki, Memory and Dementia Centre, 3rd Department of Neurology, G. Pa, University of Barcelona, University of Southampton, Department of Psychiatry [Oxford] (POWIC), University of Oxford [Oxford]-The Warneford Hospital, School of Psychology [Cardiff University], Department of Medical Sciences, UCL, Institute of Neurology [London], Washington University School of Medicine, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), School of Medecine, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], School of Life Sciences, Department of Neuroscience, Mayo Clinic Jacksonville, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Clínica Universidad de Navarra [Pamplona], Neurodegenerative Brain Diseases Group, VIB, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Brigham Young University (BYU), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, The Gertrude H Sergivesky Center, Columbia University College of Physicians and Surgeons, Genetic Epidemiology Unit, Section of Clinical and Molecular Neurogenetics, Universität zu Lübeck [Lübeck], University of Pennsylvania - Department of Pathology & Laboratory Medecine, Framingham Heart Study [Framingham, MA, USA], ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), European Project: 29845,LSH-ACC-MENTOR, University of Pennsylvania-University of Pennsylvania, Universität Bonn = University of Bonn-Institute of Human Genetics [Bonn, Germany], Universität Leipzig-Universität Leipzig, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Università degli Studi di Perugia = University of Perugia (UNIPG), Universidad Autónoma de Madrid (UAM), Università degli studi di Parma = University of Parma (UNIPR), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Universität Leipzig, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Yeshiva University- Albert Einstein College of Medicine [New York], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Università degli Studi di Milano = University of Milan (UNIMI), Saarland University Hospital (UKS), Università degli Studi di Firenze = University of Florence (UniFI), Universidade do Porto = University of Porto, University of California (UC)-University of California (UC), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Kansas Medical Center [Kansas City, KS, USA], Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UC Irvine), University of Kentucky (UK), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Department of Computer Science [Univ California Davis] (CS - UC Davis), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), University of Texas Health Science Center at San Antonio [San Antonio, Tx, USA], Universität Bonn = University of Bonn, University of Oxford-The Warneford Hospital, Medical Research Council-Cardiff University, Universität zu Lübeck = University of Lübeck [Lübeck], Epidemiology, Neurology, Gastroenterology & Hepatology, Internal Medicine, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Eberhard Karls Universität Tübingen, IRCCS 'Casa Sollievo della Sofferenza', Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas (Ciberned), University of Florida [Gainesville], University of Parma, Troubles cognitifs dégénératifs et vasculaires (U1171), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, Yeshiva University- Albert Einstein College of Medicine, Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université Polytechnique Hauts-de-France (UPHF)-Ecole Centrale de Lille-Université Polytechnique Hauts-de-France (UPHF)-Institut supérieur de l'électronique et du numérique (ISEN), Autonomous University of Barcelona (UAB), Università degli Studi di Firenze [Firenze], Universidade do Porto [Porto], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Washington University in St Louis, University of South Florida (USF), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, McGill University, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique, Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Albert Einstein College of Medicine, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Università Cattolica del S. Cuore - Catholic University of the Sacred Hearth, University of Florence (UNIFI), CIBER de Enfermedades Neurodegenerativas (CIBERNED), Universität zu Lübeck [Lübeck] - University of Lübeck [Lübeck], [ANR-10-IAIHU-06],« Investissements d'avenir » ,Agence nationale de la recherche (ANR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Department of Psychiatry, van der Lee, Sven J [0000-0003-1606-8643], Naj, Adam C [0000-0002-9621-2942], Badarinarayan, Nandini [0000-0002-6944-748X], Chouraki, Vincent [0000-0002-4698-1794], Graham, Robert R [0000-0001-7151-4277], Hoffmann, Per [0000-0002-6573-983X], Smith, Albert V [0000-0003-1942-5845], Satizabal, Claudia L [0000-0002-1115-4430], Brody, Jennifer A [0000-0001-8509-148X], Wolters, Frank J [0000-0003-2226-4050], Lupton, Michelle K [0000-0002-7274-7299], Lin, Honghuang [0000-0003-3043-3942], Adams, Hieab H [0000-0003-3687-2508], Giedraitis, Vilmantas [0000-0003-3423-2021], Pasquier, Florence [0000-0001-9880-9788], Chen, Yuning [0000-0002-7358-7055], Bossù, Paola [0000-0002-1432-0078], Ghetti, Bernardino [0000-0002-1842-8019], Yang, Qiong [0000-0002-3658-1375], Aspelund, Thor [0000-0002-7998-5433], Bullido, María J [0000-0002-6477-1117], Rivadeneira, Fernando [0000-0001-9435-9441], Rubinsztein, David C [0000-0001-5002-5263], Al-Chalabi, Ammar [0000-0002-4924-7712], Tsolaki, Magda [0000-0002-2072-8010], De Jager, Philip L [0000-0002-8057-2505], Dickson, Dennis W [0000-0001-7189-7917], Van Broeckhoven, Christine [0000-0003-0183-7665], Ikram, M Arfan [0000-0003-0372-8585], Amouyel, Philippe [0000-0001-9088-234X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Berr, Claudine, Institut de Neurosciences Translationnelles de Paris - - IHU-A-ICM2010 - ANR-10-IAHU-0006 - IAHU - VALID, and Mentoring of LifeSciHealth-Multipliers in the Accession Candidate Countries - LSH-ACC-MENTOR - 29845 - OLD
Subjects: 0301 basic medicine, Linkage disequilibrium, [SDV]Life Sciences [q-bio], Medizin, Sequence Homology, Genome-wide association study, genetics [Alzheimer Disease], metabolism [Microglia], Linkage Disequilibrium, 0302 clinical medicine, genetics [Protein Interaction Maps], genetics [Membrane Glycoproteins], Gene Frequency, Immunologic, genetics [Adaptor Proteins, Signal Transducing], Receptors, genetics [Exome], Odds Ratio, Innate, genetics [Receptors, Immunologic], Exome, Protein Interaction Maps, genetics [Genetic Predisposition to Disease], Receptors, Immunologic, ABI3 protein, human, Genetics, Adaptor Proteins, Signal Transducing, Alzheimer Disease, Amino Acid Sequence, Case-Control Studies, Gene Expression Profiling, Genetic Predisposition to Disease, Genotype, Humans, Immunity, Innate, Membrane Glycoproteins, Microglia, Phospholipase C gamma, Sequence Homology, Amino Acid, Polymorphism, Single Nucleotide, Adaptor Proteins, Single Nucleotide, 3. Good health, [SDV] Life Sciences [q-bio], Amino Acid, Settore MED/26 - NEUROLOGIA, genetics [Phospholipase C gamma], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Alzheimer's disease, Common disease-common variant, Biology, Article, 03 medical and health sciences, ddc:570, medicine, Journal Article, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Polymorphism, Allele frequency, TREM2 protein, human, TREM2, Case-control study, Signal Transducing, Immunity, medicine.disease, R1, Minor allele frequency, genetics [Immunity, Innate], 030104 developmental biology, Human medicine, 030217 neurology & neurosurgery
Abstract: International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
Published: 2017
Full Text: View/download PDF

18. [P4–533]: GENOTYPE‐DEPENDENT LONGITUDINAL TRAJECTORIES OF COGNITIVE DECLINE IN AUTOSOMAL DOMINANT ALZHEIMER's DISEASE

Author: Lars Lannfelt, Matti Viitanen, Elena Rodriguez-Vieitez, Steinunn Thordardottir, Anne Kinhult Ståhlbom, Ove Almkvist, and Caroline Graff
Subjects: 0301 basic medicine, Genetics, Epidemiology, business.industry, Health Policy, Disease, 03 medical and health sciences, Psychiatry and Mental health, Cellular and Molecular Neuroscience, 030104 developmental biology, 0302 clinical medicine, Developmental Neuroscience, Genotype, Medicine, Neurology (clinical), Geriatrics and Gerontology, Cognitive decline, business, 030217 neurology & neurosurgery
Published: 2017
Full Text: View/download PDF

19. Preclinical Cerebrospinal Fluid and Volumetric Magnetic Resonance Imaging Biomarkers in Swedish Familial Alzheimer's Disease

Author: Henrik Zetterberg, Maria Eriksdotter, Anne Kinhult Ståhlbom, Caroline Graff, Daniel Ferreira, Kaj Blennow, Eric Westman, Steinunn Thordardottir, and Ove Almkvist
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Tau protein, Prodromal Symptoms, tau Proteins, Amyloid beta-Protein Precursor, Superior temporal gyrus, Apolipoproteins E, Cognition, Atrophy, Cerebrospinal fluid, Alzheimer Disease, Presenilin-1, medicine, PSEN1, Humans, Family, Genetic Predisposition to Disease, Phosphorylation, Sweden, Amyloid beta-Peptides, Fusiform gyrus, biology, medicine.diagnostic_test, business.industry, General Neuroscience, Brain, Magnetic resonance imaging, Organ Size, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Peptide Fragments, Psychiatry and Mental health, Clinical Psychology, Mutation, biology.protein, Biomarker (medicine), Female, Geriatrics and Gerontology, business, Biomarkers
Abstract: Background It is currently believed that therapeutic interventions will be most effective when introduced at the preclinical stage of Alzheimer's disease (AD). This underlines the importance of biomarkers to detect AD pathology in vivo before clinical disease onset. Objective To examine the evolution of cerebrospinal fluid (CSF) biomarker and brain structure changes in the preclinical phase of familial AD. Methods The study included members from four Swedish families at risk for carrying an APPswe, APParc, PSEN1 H163Y, or PSEN1 I143T mutation. Magnetic resonance imaging (MRI) scans were obtained from 13 mutation carriers (MC) and 20 non-carriers (NC) and analyzed using vertex-based analyses of cortical thickness and volume. CSF was collected from 10 MC and 12 NC from familial AD families and analyzed for Aβ42, total tau (T-tau) and phospho-tau (P-tau). Results The MC had significantly lower levels of CSF Aβ42 and higher levels T-tau and P-tau than the NC. There was a trend for a decrease in Aβ42 15-20 years before expected onset of clinical symptoms, while increasing T-tau and P-tau was not found until close to the expected clinical onset. The MC had decreased volume on MRI in the left precuneus, superior temporal gyrus, and fusiform gyrus. Conclusions Aberrant biomarker levels in CSF as well as regional brain atrophy are present in preclinical familial AD, several years before the expected onset of clinical symptoms.
Published: 2014
Full Text: View/download PDF

20. Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study

Author: Thordardottir, Steinunn, primary, Rodriguez-Vieitez, Elena, additional, Almkvist, Ove, additional, Ferreira, Daniel, additional, Saint-Aubert, Laure, additional, Kinhult-Ståhlbom, Anne, additional, Thonberg, Håkan, additional, Schöll, Michael, additional, Westman, Eric, additional, Wall, Anders, additional, Eriksdotter, Maria, additional, Zetterberg, Henrik, additional, Blennow, Kaj, additional, Nordberg, Agneta, additional, and Graff, Caroline, additional
Published: 2018
Full Text: View/download PDF

21. Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation : A 22-year follow-up study

Author: Thordardottir, Steinunn, Rodriguez-Vieitez, Elena, Almkvist, Ove, Ferreira, Daniel, Saint-Aubert, Laure, Kinhult-Ståhlbom, Anne, Thonberg, Håkan, Schöll, Michael, Westman, Eric, Wall, Anders, Eriksdotter, Maria, Zetterberg, Henrik, Blennow, Kaj, Nordberg, Agneta, Graff, Caroline, Thordardottir, Steinunn, Rodriguez-Vieitez, Elena, Almkvist, Ove, Ferreira, Daniel, Saint-Aubert, Laure, Kinhult-Ståhlbom, Anne, Thonberg, Håkan, Schöll, Michael, Westman, Eric, Wall, Anders, Eriksdotter, Maria, Zetterberg, Henrik, Blennow, Kaj, Nordberg, Agneta, and Graff, Caroline
Abstract: Background: The range of onset ages within some PSEN1 families is wide, and a few cases of reduced penetrance of PSEN1 mutations have been reported. However, published data on reduced penetrance have been limited to clinical histories, often collected retrospectively and lacking biomarker information. We present a case of reduced penetrance of the PSEN1 H163Y mutation in a carrier prospectively followed for 22 years. Methods: Two brothers (A and B), both carriers of the H163Y mutation, were followed between 1995 and 2017. They underwent repeated clinical evaluations, neuropsychological assessments, and cerebrospinal fluid analyses, as well as brain imaging examinations with structural magnetic resonance, [F-18] fluorodeoxyglucose positron emission tomography, and [C-11] Pittsburgh compound B positron emission tomography. Results: Brother A was followed between 44 and 64 years of age. Cognitive symptoms due to Alzheimer's disease set in at the age of 54. Gradual worsening of symptoms resulted in admittance to a nursing home owing to dependence on others for all activities of daily living. He showed a curvilinear decline in cognitive function on neuropsychological tests, and changes on magnetic resonance imaging, positron emission tomography, and biomarkers in the cerebrospinal fluid supported a clinical diagnosis of Alzheimer's disease. Brother A died at the age of 64 and fulfilled the criteria for definitive Alzheimer's disease according to neuropathological examination results. Brother B was followed between the ages of 43 and 65 and showed no cognitive deterioration on repeated neuropsychological test occasions. In addition, no biomarker evidence of Alzheimer's disease pathology was detected, either on imaging examinations or in cerebrospinal fluid. Conclusions: The average (SD) age of symptom onset for PSEN1 H163Y is 51 +/- 7 years according to previous studies. However, we present a case of a biomarker-verified reduction in penetrance in a mutation carrier who w
Published: 2018
Full Text: View/download PDF

22. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

Author: Lambert, J. C., Ibrahim-Verbaas, C. A., Russo, G., Mayhaus, M., Lannefelt, L., Hakonarson, H., Pichler, S., Carrasquillo, M. M., Ingelsson, M., Beekly, D., Alvarez, V., Zou, F., Valladares, O., Thorton-Wells, T. A., Younkin, S. G., Coto, E., Hamilton-Nelson, K. L., Gu, W., Razquin, C., Pastor, P., Mateo, I., Owen, M. J., Faber, K. M., Jonsson, P. V., Jones, N., Combarros, O., O'Donovan, M. C., Cantwell, L. B., Soininen, H., Blacker, D., Mead, S., Mosley, T. H., Bennett, D. A., Harris, T. B., Fratiglioni, L., Smith, A. V., Holmes, C., de Bruijn, R. F., Passmore, P., Montine, T. J., Bettens, K., Rotter, J. I., Brice, A., Morgan, K., Foroud, T. M., Kukull, W. A., Chouraki, V., Hannequin, D., Powell, J. F., Nalls, M. A., Ritchie, K., Lunetta, K. L., Kauwe, J. S., Boerwinkle, E., Riemenschneider, M., Boada, M., Hiltuenen, M., Thomas, C., Martin, E. R., Schmidt, R., Rujescu, D., Wang, L. S., Dartigues, J. F., Mayeux, R., Tzourio, C., Hofman, A., Nöthen, M. M., Graff, C., Ikram, M. A., Psaty, B. M., Jones, L., Haines, J. L., Holmans, P. A., Lathrop, M., Pericak-Vance, M. A., Launer, L. J., Farrer, L. A., van Duijn, C. M., Van Broeckhoven, C., Zelenika, D., Moskvina, V., Seshadri, S., Williams, J., Schellenberg, G. D., Amouyel, P., Alpérovitch, A., Boland, A., Delépoine, M., Dubois, B., Duron, E., Vardarajan, B. N., Epelbaum, J., Van Cauwenberghe, C., Engelborghs, S., Vandenberghe, R., De Deyn, P. P., Ferri, R., Romano, C., Caltagirone, C., Orfei, M. D., Ciaramella, A., Kamatani, Y., Scarpini, E., Fenoglio, C., Siciliano, G., Bonuccelli, U., Bagnoli, S., Bracco, L., Bessi, V., Cecchetti, R., Bastgiani, P., Squassina, A., Harold, D., Lin, C. F., Seripa, D., Frank-García, A., Sastre, I., Blesa, R., Alcolea, D., Suárez-Clavet, M., Sánchez-Juan, P., Muñoz Fernandez, C., Aladro Benito, Y., Thonberg, H., Gerrish, A., Forshell, C., Lilus, L., Kinhult-Ståhlbom, A., Giedraitis, V., Kilander, L., Brundin, R. M., Concari, L., Helisalmi, S., Koivisto, A. M., Haapasalo, A., Schmidt, H., Solfrizzi, V., Frisardi, V., Ott, J., Carney, R. M., Mash, D. C., Albert, M. S., Albin, R. L., Apostolova, L. G., Arnold, S. E., Barmada, M. M., Kunkle, B., Barnes, L. L., Beach, T. G., Bigio, E. H., Bird, T. D., Boeve, B. F., Bowen, J. D., Boxer, A., Burk, J. R., Cairns, N. J., Cao, C., Dunstan, M. L., Carlson, C. S., Carroll, S. L., Chibnik, L. B., Chui, H. C., Clark, D. G., Corneveaux, J., Cribbs, D. G., DeCarli, C., DeKosky, S. T., Demirci, F. Y., Ruiz, A., Dick, M., Dickson, D. W., Duara, R., Ertekin-Taner, N., Fallon, K. B., Farlow, M. R., Ferris, S., Frosch, M. P., Galasko, G. R., Ganguli, M., Bihoreau, M. T., Gearing, M., Geschwind, D. H., Ghetti, B., Gilman, S., Glass, J. D., Growdon, J. H., Hamilton, R. L., Harrell, L. E., Head, E., Honig, L. S., Choi, S. H., Hulette, C. M., Hyman, B. T., Jarvik, G. P., Jicha, G. A., Jin, L. W., Karydas, A., Kaye, J. A., Kim, R., Koo, E. H., Reitz, C., Kowall, N. W., Kramer, J. H., Kramer, P., LaFerla, F. M., Lah, J. J., Levernez, J. B., Levey, A. I., Li, G., Lieberman, A. P., Lyketsos, C. G., Pasquier, F., Mack, W. J., Marson, D. C., Martiniuk, F., Masliah, E., McCormick, W. C., McCurry, S. M., McDavid, A. N., McKee, A. C., Mesulam, M., Miller, B. L., Naj, A. C., Cruchaga, C., Miller, C. A., Miller, J. W., Morris, J. C., Murrell, J. R., Olichney, J. M., Pankratz, V. S., Parasi, J. E., Peskind, E., Peterson, R. C., Pierce, A., Craig, D., Poon, W. W., Potter, H., Quinn, J. F., Raj, A., Raskind, M., Raiman, E. M., Reisberg, B., Ringman, J. M., Roberson, E. D., Rosen, H. J., Amin, N., Rosenberg, R. N., Sano, M., Saykin, A. J., Schneider, J. A., Schneider, L. S., Seely, W. W., Smith, A. G., Sonnen, J. A., Spina, S., Stern, R. A., Berr, C., Tanzi, R. E., Trojanowski, J. Q., Troncoso, J. C., Van Deerlin, V. M., Van Eldik, L. J., Vinters, H. V., Vonsattel, J. P., Weintraub, S., Welsh-Bohmer, K. A., Williamson, J., Lopez, O. L., Woltjer, R. L., Yu, C. E., Barber, R., Au, R., Wolf, P. A., Beiser, A., Debette, S., Yang, Q., Weinstein, G., Johnson, A. D., De Jager, P. L., Wang, J., Uitterlinden, A. G., Rivadeneira, F., Koudstgaal, P. J., Longstreth, W. T., Becker, J. T., Kuller, L. H., Lumley, T., Rice, K., Garcia, M., Deramecourt, V., Aspelund, T., Marksteiner, J. J., Dal-Bianco, P., Töglhofer, A. M., Freudenberger, P., Ransmayr, G., Benke, T., Toeglhofer, A. M., Bressler, J., Breteler, M. M., Johnston, J. A., Fornage, M., Hernández, I., Rosende Roca, M., Ana Mauleón, M., Alegrat, M., RamÍrez-Lorca, R., González-Perez, A., Chapman, J., Stretton, A., Morgan, A., Evans, D., Kehoe, P. G., Medway, C., Lord, J., Turton, J., Hooper, N. M., Vardy, E., Warren, J. D., Schott, J. M., Uphill, J., Ryan, N., Lovestone, S., Rossor, M., Ben-Shlomo, Y., Makrina, D., Gkatzima, O., Lupton, M., Koutroumani, M., Avramidou, D., Germanou, A., Jessen, F., Riedel-Heller, S., Sims, R., Letenneur, L., Dichgans, M., Heun, R., Kölsch, H., Schürmann, B., Herold, C., Lacour, A., Drichel, D., Hoffman, P., Kornhuber, J., Morón, F. J., Feulner, T., van den Bussche, H., Lawlor, B., Lynch, A., Mann, D., Smith, A. D., Warden, D., Wilcock, G., Heuser, I., Wiltgang, J., Rubinsztein, D. C., Frölich, L., Hüll, M., Mayo, K., Livingston, G., Bass, N. J., Gurling, H., McQuillen, A., Gwilliam, R., Deloukas, P., Al-Chalabi, A., Eiriksdottir, G., Shaw, C. E., Singleton, A. B., Guerreiro, R., Jöckel, K. H., Klopp, N., Wichmann, H. E., Graff-Radford, N. R., Ma, L., Bisceglio, G., Sleegers, K., Fisher, E., Warner, N., Pickering-Brown, S., Becker, Tim, Goate, A. M., Fiévet, N., Huentelman, M. W., Gill, M., Brown, K., Bellenguez, C., Kamboh, M. I., Keller, L., Barberger-Gateau, P., McGuiness, B., Larson, E. B., Green, R., Myers, A. J., Dufouil, C., Todd, S., Wallon, D., DeStafano, A. L., Love, S., Rogaeva, E., Gallacher, J., St George-Hyslop, P., Clarimon, J., Lleo, A., Bayer, A., Tsuang, D. W., Yu, L., Tsolaki, M., Bis, J. C., Bossù, P., Spalletta, G., Proitsi, P., Collinge, J., Sorbi, S., Sanchez-Garcia, F., Fox, N. C., Hardy, J., Deniz Naranjo, M. C., Bosco, P., Beecham, G. W., Clarke, R., Brayne, C., Galimberti, D., Mancuso, M., Matthews, F., Initiative, European Alzheimer's Disease, Disease, Genetic and Environmental Risk in Alzheimer's, Consortium, Alzheimer's Disease Genetic, Epidemiology, Cohorts for Heart and Aging Research in Genomic, Moebus, S., Grenier-Boley, B., Mecocci, P., Del Zompo, M., Maier, W., Hampel, H., Pilotto, A., Bullido, M., Panza, F., Caffarra, P., Nacmias, B., Gilbert, J. R., Neurology, Radiology & Nuclear Medicine, and Epidemiology
Subjects: Male, Apolipoprotein E, epidemiology [Alzheimer Disease], SORL1, Medizin, genetics [Alzheimer Disease], Genome-wide association study, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, PICALM, Cohort Studies, Alzheimer Disease, ddc:570, PSEN2, Genetics, medicine, Humans, Genetic Predisposition to Disease, Age of Onset, Aged, Genetic association, Aged, 80 and over, Middle Aged, medicine.disease, Genetic Loci, Case-Control Studies, Female, Human medicine, Alzheimer's disease, statistics & numerical data [Genome-Wide Association Study], Genome-Wide Association Study
Abstract: Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 x 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.
Published: 2013
Full Text: View/download PDF

23. The effects of different familial Alzheimer’s disease mutations on APP processing in vivo

Author: Henrik Zetterberg, Kaj Blennow, Håkan Thonberg, Maria Eriksdotter, Steinunn Thordardottir, Ove Almkvist, Anne Kinhult Ståhlbom, and Caroline Graff
Subjects: 0301 basic medicine, medicine.medical_specialty, Heterozygote, Neurology, Cognitive Neuroscience, Clinical Neurology, Disease, Pathogenesis, 03 medical and health sciences, Amyloid beta-Protein Precursor, 0302 clinical medicine, Cerebrospinal fluid, Apolipoproteins E, Mutation Carrier, Alzheimer Disease, medicine, Amyloid precursor protein, PSEN1, Genetics, Presenilin-1, Humans, Family, biology, business.industry, Research, Middle Aged, Pathophysiology, 030104 developmental biology, Cross-Sectional Studies, Immunology, Mutation, biology.protein, Neurology (clinical), business, Neuroscience, Alzheimer’s disease, 030217 neurology & neurosurgery, Biomarkers
Abstract: Background Disturbed amyloid precursor protein (APP) processing is considered to be central to the pathogenesis of Alzheimer’s disease (AD). The autosomal dominant form of the disease, familial AD (FAD), may serve as a model for the sporadic form of AD. In FAD the diagnosis of AD is reliable and presymptomatic individuals carrying FAD mutations can give valuable insights into the earliest stages of the disease where therapeutic interventions are thought to be the most effective. Methods In the current cross-sectional study, products of APP processing (e.g., sAPPα, sAPPβ, Aβ38, Aβ40 and Aβ42) were measured in the cerebrospinal fluid (CSF) of individuals carrying one of three FAD mutations, APPswe (p.KM670/671NL), APParc (p.E693G) and PSEN1 (p.H163Y), as well as in non-mutation carriers from the same families. Results We observed pathological APP processing in presymptomatic carriers of FAD mutations, with different profiles of APP and Aβ isoforms in the three mutation carrier groups, APPswe (p.KM670/671NL), APParc (p.E693G) and PSEN1 (p.H163Y), except for the well-established decrease in CSF Aβ42 that was found with all mutations. Conclusions These findings add to the current evidence that AD pathophysiology differs between disease-causing mutations and can be monitored in the presymptomatic disease stage by CSF analyses. This may also be important from a therapeutic standpoint, by opening a window to monitor effects of disease-modifying drugs on AD pathophysiology.
Published: 2017

24. Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer’s Disease

Author: Lars-Olof Wahlund, Elena Rodriguez-Vieitez, Matti Viitanen, Anne Kinhult-Ståhlbom, Lars Lannfelt, Anne M. Remes, Hans Basun, Kaarina Amberla, Ove Almkvist, Steinunn Thordardottir, Lena Lilius, Karin Axelman, and Caroline Graff
Subjects: Adult, Male, Oncology, Heterozygote, medicine.medical_specialty, Memory, Episodic, Disease, ta3112, 050105 experimental psychology, Amyloid beta-Protein Precursor, Executive Function, 03 medical and health sciences, 0302 clinical medicine, Mutation Carrier, Alzheimer Disease, Predictive Value of Tests, Internal medicine, Presenilin-1, medicine, Humans, Cognitive Dysfunction, 0501 psychology and cognitive sciences, Effects of sleep deprivation on cognitive performance, Cognitive decline, Aged, Family Health, Sweden, Geriatrics, General Neuroscience, 05 social sciences, Cognition, Middle Aged, ta3124, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Mutation, Mutation (genetic algorithm), Disease Progression, Visual Perception, Female, Neurology (clinical), Age of onset, 030217 neurology & neurosurgery
Abstract: Objectives: The aim of this study was to investigate cognitive performance including preclinical and clinical disease course in carriers and non-carriers of autosomal-dominant Alzheimer’s disease (adAD) in relation to multiple predictors, that is, linear and non-linear estimates of years to expected clinical onset of disease, years of education and age. Methods: Participants from five families with early-onset autosomal-dominant mutations (Swedish and Arctic APP, PSEN1 M146V, H163Y, and I143T) included 35 carriers (28 without dementia and 7 with) and 44 non-carriers. All participants underwent a comprehensive clinical evaluation, including neuropsychological assessment at the Memory Clinic, Karolinska University Hospital at Huddinge, Stockholm, Sweden. The time span of disease course covered four decades of the preclinical and clinical stages of dementia. Neuropsychological tests were used to assess premorbid and current global cognition, verbal and visuospatial functions, short-term and episodic memory, attention, and executive function. Results: In carriers, the time-related curvilinear trajectory of cognitive function across disease stages was best fitted to a formulae with three predictors: years to expected clinical onset (linear and curvilinear components), and years of education. In non-carriers, the change was minimal and best predicted by two predictors: education and age. The trajectories for carriers and non-carriers began to diverge approximately 10 years before the expected clinical onset in episodic memory, executive function, and visuospatial function. Conclusions: The curvilinear trajectory of cognitive functions across disease stages was mimicked by three predictors in carriers. In episodic memory, executive and visuospatial functions, the point of diverging trajectories occurred approximately 10 years ahead of the clinical onset compared to non-carriers. (JINS, 2017, 23, 195–203)
Published: 2017
Full Text: View/download PDF

25. Evaluation of the BOADICEA risk assessment model in women with a family history of breast cancer

Author: Hemming Johansson, Anna von Wachenfeldt, Brita Arver, Annelie Liljegren, and Anne Kinhult Ståhlbom
Subjects: Adult, Oncology, Heterozygote, Cancer Research, medicine.medical_specialty, Mutation rate, Breast Neoplasms, Risk Assessment, Breast cancer, Mutation Rate, Internal medicine, Epidemiology, Genetics, medicine, Humans, Genetics(clinical), Genetic Predisposition to Disease, Genetic Testing, Prospective Studies, Family history, skin and connective tissue diseases, Prospective cohort study, Genetics (clinical), Genetic testing, BRCA2 Protein, medicine.diagnostic_test, Receiver operating characteristic, BRCA1 Protein, business.industry, Incidence, Incidence (epidemiology), Middle Aged, Models, Theoretical, BRCA1, medicine.disease, BRCA2, Carcinoma, Intraductal, Noninfiltrating, ROC Curve, Mutation, Original Article, BOADICEA, Female, business
Abstract: The ability of the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model to predict BRCA1 and BRCA2 mutations and breast cancer incidence in women with a family history of breast cancer was evaluated. Observed mutations in 263 screened families were compared to retrospective predictions. Similarly, observed breast cancers in 640 women were compared to retrospective predictions of breast cancer incidence. The ratios of observed to expected number of BRCA1- , BRCA2- and BRCA(1 or 2) mutations were 1.43 (95% CI 1.05-1.90), 0.63 (95% CI 0.34-1.08), and 1.12 (95% CI 0.86-1.44), showing a significant underestimation of BRCA1 mutations. Discrimination between carriers and non-carriers as measured by area under the receiver operating characteristic (ROC) curve was 0.83 (95% CI 0.76-0.88). The ratio of observed to expected number of invasive breast cancers was 1.41 (0.91-2.08). The corresponding area under the ROC curve for prediction of invasive breast cancer at individual level was 0.62 (95% CI 0.52-0.73). In conclusion, the BOADICEA model can predict the total prevalence of BRCA(1 or 2) mutations and the incidence of invasive breast cancers. The mutation probability as generated by BOADICEA can be used clinically as a guideline for screening, and thus decrease the proportion of negative mutation analyses. Likewise, individual breast cancer risks can be used for selecting women whose risk of breast cancer indicates follow-up. Application of local mutation frequencies of BRCA1 and BRCA2 could improve the ability to distinguish between the two genes.
Published: 2011
Full Text: View/download PDF

26. Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer's Disease

Author: Almkvist, Ove, Rodriguez-Vieitez, Elena, Thordardottir, Steinunn, Amberla, Kaarina, Axelman, Karin, Basun, Hans, Kinhult-Ståhlbom, Anne, Lilius, Lena, Remes, Anne, Wahlund, Lars-Olof, Viitanen, Matti, Lannfelt, Lars, Graff, Caroline, Almkvist, Ove, Rodriguez-Vieitez, Elena, Thordardottir, Steinunn, Amberla, Kaarina, Axelman, Karin, Basun, Hans, Kinhult-Ståhlbom, Anne, Lilius, Lena, Remes, Anne, Wahlund, Lars-Olof, Viitanen, Matti, Lannfelt, Lars, and Graff, Caroline
Abstract: Objectives: The aim of this study was to investigate cognitive performance including preclinical and clinical disease course in carriers and non-carriers of autosomal-dominant Alzheimer's disease (adAD) in relation to multiple predictors, that is, linear and non-linear estimates of years to expected clinical onset of disease, years of education and age. Methods: Participants from five families with early-onset autosomal-dominant mutations (Swedish and Arctic APP, PSEN1 M146V, H163Y, and I143T) included 35 carriers (28 without dementia and 7 with) and 44 non-carriers. All participants underwent a comprehensive clinical evaluation, including neuropsychological assessment at the Memory Clinic, Karolinska University Hospital at Huddinge, Stockholm, Sweden. The time span of disease course covered four decades of the preclinical and clinical stages of dementia. Neuropsychological tests were used to assess premorbid and current global cognition, verbal and visuospatial functions, short-term and episodic memory, attention, and executive function. Results: In carriers, the time-related curvilinear trajectory of cognitive function across disease stages was best fitted to a formulae with three predictors: years to expected clinical onset (linear and curvilinear components), and years of education. In non-carriers, the change was minimal and best predicted by two predictors: education and age. The trajectories for carriers and non-carriers began to diverge approximately 10 years before the expected clinical onset in episodic memory, executive function, and visuospatial function. Conclusions: The curvilinear trajectory of cognitive functions across disease stages was mimicked by three predictors in carriers. In episodic memory, executive and visuospatial functions, the point of diverging trajectories occurred approximately 10 years ahead of the clinical onset compared to non-carriers.
Published: 2017
Full Text: View/download PDF

27. White matter changes in familial Alzheimer's disease

Author: Xinjun Li, Ove Almkvist, Lars-Olof Wahlund, Eric Westman, Steinunn Thordardottir, Kaj Blennow, Anne Kinhult Ståhlbom, and Caroline Graff
Subjects: Adult, Male, medicine.medical_specialty, Pathology, Gene mutation, Grey matter, Neuropsychological Tests, behavioral disciplines and activities, White matter, Alzheimer Disease, PSEN2, Fractional anisotropy, Internal Medicine, medicine, PSEN1, Humans, Psychiatry, business.industry, Superior longitudinal fasciculus, Middle Aged, White Matter, medicine.anatomical_structure, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Female, business, Diffusion MRI
Abstract: Background Familial Alzheimer's disease (FAD) resulting from gene mutations in PSEN1, PSEN2 and APP is associated with changes in the brain. Objective The aim of this study was to investigate changes in grey matter (GM), white matter (WM) and the cerebrospinal fluid (CSF) in FAD. Subjects Ten mutation carriers (MCs) with three different mutations in PSEN1 and APP and 20 noncarriers (NCs) were included in the study. Three MCs were symptomatic and seven were presymptomatic (pre-MCs). Methods Whole-brain GM volume as well as fractional anisotropy (FA) and mean diffusivity (MD) using voxel-based morphometry and tract-based spatial statistics analyses, respectively, were compared between MCs and NCs. FA and MD maps were obtained from diffusion tensor imaging. Results A significant increase in MD was found in the left inferior longitudinal fasciculus, cingulum and bilateral superior longitudinal fasciculus in pre-MCs compared with NCs. After inclusion of the three symptomatic MCs in the analysis, the regions became wider. The mean MD of these regions showed significant negative correlation with the CSF level of Aβ42, and positive correlations with P-tau181p and T-tau. No differences were observed in GM volume and FA between the groups. Conclusions The results of this study suggest that FAD gene mutations affect WM diffusivity before changes in GM volume can be detected. The WM changes observed were related to changes in the CSF, with similar patterns previously observed in sporadic Alzheimer's disease.
Published: 2015

28. The effects of different familial Alzheimer’s disease mutations on APP processing in vivo

Author: Thordardottir, Steinunn, primary, Kinhult Ståhlbom, Anne, additional, Almkvist, Ove, additional, Thonberg, Håkan, additional, Eriksdotter, Maria, additional, Zetterberg, Henrik, additional, Blennow, Kaj, additional, and Graff, Caroline, additional
Published: 2017
Full Text: View/download PDF

29. Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer’s Disease

Author: Almkvist, Ove, primary, Rodriguez-Vieitez, Elena, additional, Thordardottir, Steinunn, additional, Amberla, Kaarina, additional, Axelman, Karin, additional, Basun, Hans, additional, Kinhult-Ståhlbom, Anne, additional, Lilius, Lena, additional, Remes, Anne, additional, Wahlund, Lars-Olof, additional, Viitanen, Matti, additional, Lannfelt, Lars, additional, and Graff, Caroline, additional
Published: 2017
Full Text: View/download PDF

30. P1–203: The effects of gene mutations on the cerebrospinal fluid levels of soluble amyloid precursor proteins in familial Alzheimer's disease

Author: Ove Almkvist, Anne Kinhult-Ståhlbom, Steinunn Thordardottir, Kaj Blennow, Caroline Graff, Henrik Zetterberg, and Maria Eriksdotter Jönhagen
Subjects: Amyloid, biology, Epidemiology, business.industry, Health Policy, BACE1-AS, P3 peptide, Gene mutation, Molecular biology, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Transthyretin, Cerebrospinal fluid, Developmental Neuroscience, Familial Alzheimer's disease, biology.protein, Medicine, Neurology (clinical), Geriatrics and Gerontology, business
Published: 2013
Full Text: View/download PDF

31. A pan-European study of the C9orf72 repeat associated with FTLD: geographic prevalence, genomic instability, and intermediate repeats

Author: Julie, van der Zee, Ilse, Gijselinck, Lubina, Dillen, Tim, Van Langenhove, Jessie, Theuns, Sebastiaan, Engelborghs, Stéphanie, Philtjens, Mathieu, Vandenbulcke, Kristel, Sleegers, Anne, Sieben, Veerle, Bäumer, Githa, Maes, Ellen, Corsmit, Barbara, Borroni, Alessandro, Padovani, Silvana, Archetti, Robert, Perneczky, Janine, Diehl-Schmid, Alexandre, de Mendonça, Gabriel, Miltenberger-Miltenyi, Sónia, Pereira, José, Pimentel, Benedetta, Nacmias, Silvia, Bagnoli, Sandro, Sorbi, Caroline, Graff, Huei-Hsin, Chiang, Marie, Westerlund, Raquel, Sanchez-Valle, Albert, Llado, Ellen, Gelpi, Isabel, Santana, Maria Rosário, Almeida, Beatriz, Santiago, Giovanni, Frisoni, Orazio, Zanetti, Cristian, Bonvicini, Matthis, Synofzik, Walter, Maetzler, Jennifer Müller, Vom Hagen, Ludger, Schöls, Michael T, Heneka, Frank, Jessen, Radoslav, Matej, Eva, Parobkova, Gabor G, Kovacs, Thomas, Ströbel, Stayko, Sarafov, Ivailo, Tournev, Albena, Jordanova, Adrian, Danek, Thomas, Arzberger, Gian Maria, Fabrizi, Silvia, Testi, Eric, Salmon, Patrick, Santens, Jean-Jacques, Martin, Patrick, Cras, Rik, Vandenberghe, Peter Paul, De Deyn, Marc, Cruts, Christine, Van Broeckhoven, Peter P, De Deyn, Jennifer, Müller Vom Hagen, Alfredo, Ramirez, Delia, Kurzwelly, Carmen, Sachtleben, Wolfgang, Mairer, Clara, Firmo, Anna, Antonell, Jose, Molinuevo, Anne, Kinhult Ståhlbom, Håkan, Thonberg, Inger, Nennesmo, Anne, Börjesson-Hanson, Valentina, Bessi, Irene, Piaceri, Maria, Helena Ribeiro, Maria, Rosário Almeida, Catarina, Oliveira, João, Massano, Carolina, Garret, Paula, Pires, Adrian, Danel, Gian, Maria Fabrizi, Sergio, Ferrari, Tiziana, Cavallaro, European Early-Onset Dementia (EOD) Consortium, Clinical sciences, Neurology, Physiotherapy, Human Physiology and Anatomy, and Pathologic Biochemistry and Physiology
Subjects: epidemiology [Finland], Finland/epidemiology, Frontotemporal Lobar Degeneration/epidemiology, genetics [Alzheimer Disease], epidemiology [Spain], genetics [Chromosomes, Human, Pair 9], methods [Genome-Wide Association Study], Cohort Studies, 0302 clinical medicine, Replication slippage, C9orf72, Germany, Prevalence, Age of Onset, epidemiology [Frontotemporal Lobar Degeneration], Genetics (clinical), Finland, Research Articles, FTLD, repeat expansion, intermediate alleles, European early-onset dementia consortium, Medicine(all), Genetics, Aged, 80 and over, 0303 health sciences, DNA Repeat Expansion, epidemiology [Europe], Frontotemporal lobar degeneration, Middle Aged, Europe, Proteins/genetics, Genome-Wide Association Study/methods, Spain/epidemiology, genetics [Frontotemporal Lobar Degeneration], Chromosomes, Human, Pair 9, Adult, Molecular Sequence Data, Chromosomes, Human, Pair 9/genetics, Germany/epidemiology, epidemiology [Germany], Biology, Genomic Instability, Europe/epidemiology, 03 medical and health sciences, Alzheimer Disease, medicine, Humans, ddc:610, Indel, Alleles, 030304 developmental biology, Aged, Sweden, Alzheimer Disease/genetics, European Early-Onset Dementia consortium, Base Sequence, C9orf72 Protein, Haplotype, Proteins, epidemiology [Sweden], medicine.disease, genetics [Proteins], Sweden/epidemiology, Haplotypes, Spain, Human medicine, C9orf72 protein, human, Frontotemporal Lobar Degeneration, Trinucleotide repeat expansion, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: We assessed the geographical distribution of C9orf72 G4C2 expansions in a pan-European frontotemporal lobar degeneration (FTLD) cohort (n = 1205), ascertained by the European Early-Onset Dementia (EOD) consortium. Next, we performed a meta-analysis of our data and that of other European studies, together 2,668 patients from 15 Western European countries. The frequency of the C9orf72 expansions in Western Europe was 9.98% in overall FTLD, with 18.52% in familial, and 6.26% in sporadic FTLD patients. Outliers were Finland and Sweden with overall frequencies of respectively 29.33% and 20.73%, but also Spain with 25.49%. In contrast, prevalence in Germany was limited to 4.82%. In addition, we studied the role of intermediate repeats (7 to 24 repeat units), which are strongly correlated with the risk haplotype, on disease and C9orf72 expression. In vitro reporter gene expression studies demonstrated significantly decreased transcriptional activity of C9orf72 with increasing number of normal repeat units, indicating that intermediate repeats might act as predisposing alleles and in favor of the loss-of-function disease mechanism. Further, we observed a significantly increased frequency of short indels in the GC-rich low complexity sequence (LCS) adjacent to the G4C2 repeat in C9orf72 expansion carriers (p < 0.001) with the most common indel creating one long contiguous imperfect G4C2 repeat which is likely more prone to replication slippage and pathological expansion.
Published: 2012
Full Text: View/download PDF

32. P1‐410: Multitracer PET studies in kindreds with early‐onset familial Alzheimer gene mutations

Author: Michael Schöll, Henry Engler, Caroline Graff, Ove Almkvist, Anders Wall, Agneta Nordberg, and Anne Kinhult-Ståhlbom
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, business.industry, Health Policy, Cancer research, Medicine, Neurology (clinical), Geriatrics and Gerontology, Gene mutation, business, Early onset
Published: 2010
Full Text: View/download PDF

33. P1–203: The effects of gene mutations on the cerebrospinal fluid levels of soluble amyloid precursor proteins in familial Alzheimer's disease

Author: Thordardottir, Steinunn, primary, Kinhult‐Ståhlbom, Anne, additional, Almkvist, Ove, additional, Jonhagen, Maria Eriksdotter, additional, Zetterberg, Henrik, additional, Blennow, Kaj, additional, and Graff, Caroline, additional
Published: 2013
Full Text: View/download PDF

34. Multitracer PET studies in kindreds with early-onset familial Alzheimer gene mutations

Author: Schöll, Michael, primary, Almkvist, Ove, additional, Wall, Anders, additional, Engler, Henry, additional, Kinhult-Ståhlbom, Anne, additional, Graff, Caroline, additional, and Nordberg, Agneta, additional
Published: 2010
Full Text: View/download PDF

35. Reduced penetrance of the <italic>PSEN1</italic> H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study.

Author: Thordardottir, Steinunn, Rodriguez-Vieitez, Elena, Almkvist, Ove, Ferreira, Daniel, Saint-Aubert, Laure, Kinhult-Ståhlbom, Anne, Thonberg, Håkan, Schöll, Michael, Westman, Eric, Wall, Anders, Eriksdotter, Maria, Zetterberg, Henrik, Blennow, Kaj, Nordberg, Agneta, and Graff, Caroline
Subjects: GENETICS of Alzheimer's disease, GENETIC mutation, ALZHEIMER'S disease diagnosis, FLUORODEOXYGLUCOSE F18, POSITRON emission tomography, CLINICAL trials
Abstract: Background: The range of onset ages within some PSEN1 families is wide, and a few cases of reduced penetrance of PSEN1 mutations have been reported. However, published data on reduced penetrance have been limited to clinical histories, often collected retrospectively and lacking biomarker information. We present a case of reduced penetrance of the PSEN1 H163Y mutation in a carrier prospectively followed for 22 years. Methods: Two brothers (A and B), both carriers of the H163Y mutation, were followed between 1995 and 2017. They underwent repeated clinical evaluations, neuropsychological assessments, and cerebrospinal fluid analyses, as well as brain imaging examinations with structural magnetic resonance, [18F]fluorodeoxyglucose positron emission tomography, and [11C]Pittsburgh compound B positron emission tomography. Results: Brother A was followed between 44 and 64 years of age. Cognitive symptoms due to Alzheimer's disease set in at the age of 54. Gradual worsening of symptoms resulted in admittance to a nursing home owing to dependence on others for all activities of daily living. He showed a curvilinear decline in cognitive function on neuropsychological tests, and changes on magnetic resonance imaging, positron emission tomography, and biomarkers in the cerebrospinal fluid supported a clinical diagnosis of Alzheimer's disease. Brother A died at the age of 64 and fulfilled the criteria for definitive Alzheimer's disease according to neuropathological examination results. Brother B was followed between the ages of 43 and 65 and showed no cognitive deterioration on repeated neuropsychological test occasions. In addition, no biomarker evidence of Alzheimer's disease pathology was detected, either on imaging examinations or in cerebrospinal fluid. Conclusions: The average (SD) age of symptom onset for PSEN1 H163Y is 51 ± 7 years according to previous studies. However, we present a case of a biomarker-verified reduction in penetrance in a mutation carrier who was still symptom-free at the age of 65. This suggests that other genetic, epigenetic, and/or environmental factors modify the onset age. [ABSTRACT FROM AUTHOR]
Published: 2018
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

35 results on '"Kinhult Ståhlbom, A"'

1. Extended genetic analysis and tumor characteristics in over 4600 women with suspected hereditary breast and ovarian cancer

2. Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

3. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

4. Whole-body MRI within a surveillance program for carriers with clinically actionable germline TP53 variants - the Swedish constitutional TP53 study SWEP53

5. Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study

6. Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores (Nature Communications, (2021), 12, 1, (3417), 10.1038/s41467-021-22491-8)

7. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

8. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

9. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

10. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

11. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

12. The Effects of Gene Mutations on Default Mode Network in Familial Alzheimer’s Disease

13. Additional file 3: of Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study

14. Additional file 1: of Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study

15. Additional file 2: of Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study

16. Prospective blinded surveillance screening of Swedish women with increased hereditary risk of breast cancer

17. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

18. [P4–533]: GENOTYPE‐DEPENDENT LONGITUDINAL TRAJECTORIES OF COGNITIVE DECLINE IN AUTOSOMAL DOMINANT ALZHEIMER's DISEASE

19. Preclinical Cerebrospinal Fluid and Volumetric Magnetic Resonance Imaging Biomarkers in Swedish Familial Alzheimer's Disease

20. Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study

21. Reduced penetrance of the PSEN1 H163Y autosomal dominant Alzheimer mutation : A 22-year follow-up study

22. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

23. The effects of different familial Alzheimer’s disease mutations on APP processing in vivo

24. Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer’s Disease

25. Evaluation of the BOADICEA risk assessment model in women with a family history of breast cancer

26. Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer's Disease

27. White matter changes in familial Alzheimer's disease

28. The effects of different familial Alzheimer’s disease mutations on APP processing in vivo

29. Predicting Cognitive Decline across Four Decades in Mutation Carriers and Non-carriers in Autosomal-Dominant Alzheimer’s Disease

30. P1–203: The effects of gene mutations on the cerebrospinal fluid levels of soluble amyloid precursor proteins in familial Alzheimer's disease

31. A pan-European study of the C9orf72 repeat associated with FTLD: geographic prevalence, genomic instability, and intermediate repeats

32. P1‐410: Multitracer PET studies in kindreds with early‐onset familial Alzheimer gene mutations

33. P1–203: The effects of gene mutations on the cerebrospinal fluid levels of soluble amyloid precursor proteins in familial Alzheimer's disease

34. Multitracer PET studies in kindreds with early-onset familial Alzheimer gene mutations

35. Reduced penetrance of the <italic>PSEN1</italic> H163Y autosomal dominant Alzheimer mutation: a 22-year follow-up study.

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

35 results on '"Kinhult Ståhlbom, A"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources