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2. Centenarian clocks: epigenetic clocks for validating claims of exceptional longevity

Author

Dec, Eric, Clement, James, Cheng, Kaiyang, Church, George M, Fossel, Michael B, Rehkopf, David H, Rosero-Bixby, Luis, Kobor, Michael S, Lin, David TS, Lu, Ake T, Fei, Zhe, Guo, Wei, Chew, Yap Ching, Yang, Xiaojing, Putra, Sulistyo E Dwi, Reiner, Alex P, Correa, Adolfo, Vilalta, Adrian, Pirazzini, Chiara, Passarino, Giuseppe, Monti, Daniela, Arosio, Beatrice, Garagnani, Paolo, Franceschi, Claudio, and Horvath, Steve

Subjects
Biological Sciences, Genetics, Aging, Clinical Research, Human Genome, Aged, 80 and over, Humans, Longevity, Centenarians, DNA Methylation, Epigenesis, Genetic, Centenarian clocks, Epigenetic clocks, Clinical sciences
Abstract

Claims surrounding exceptional longevity are sometimes disputed or dismissed for lack of credible evidence. Here, we present three DNA methylation-based age estimators (epigenetic clocks) for verifying age claims of centenarians. The three centenarian clocks were developed based on n = 7039 blood and saliva samples from individuals older than 40, including n = 184 samples from centenarians, 122 samples from semi-supercentenarians (aged 105 +), and 25 samples from supercentenarians (aged 110 +). The oldest individual was 115 years old. Our most accurate centenarian clock resulted from applying a neural network model to a training set composed of individuals older than 40. An epigenome-wide association study of age in different age groups revealed that age effects in young individuals (age  90). We present a chromatin state analysis of age effects in centenarians. The centenarian clocks are expected to be useful for validating claims surrounding exceptional old age.

Published
2023

6. 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
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7. New insights into the genetic etiology of Alzheimer’s disease and related dementias

Author

Bellenguez, Céline, Küçükali, Fahri, Jansen, Iris E, Kleineidam, Luca, Moreno-Grau, Sonia, Amin, Najaf, Naj, Adam C, Campos-Martin, Rafael, Grenier-Boley, Benjamin, Andrade, Victor, Holmans, Peter A, Boland, Anne, Damotte, Vincent, van der Lee, Sven J, Costa, Marcos R, Kuulasmaa, Teemu, Yang, Qiong, de Rojas, Itziar, Bis, Joshua C, Yaqub, Amber, Prokic, Ivana, Chapuis, Julien, Ahmad, Shahzad, Giedraitis, Vilmantas, Aarsland, Dag, Garcia-Gonzalez, Pablo, Abdelnour, Carla, Alarcón-Martín, Emilio, Alcolea, Daniel, Alegret, Montserrat, Alvarez, Ignacio, Álvarez, Victoria, Armstrong, Nicola J, Tsolaki, Anthoula, Antúnez, Carmen, Appollonio, Ildebrando, Arcaro, Marina, Archetti, Silvana, Pastor, Alfonso Arias, Arosio, Beatrice, Athanasiu, Lavinia, Bailly, Henri, Banaj, Nerisa, Baquero, Miquel, Barral, Sandra, Beiser, Alexa, Pastor, Ana Belén, Below, Jennifer E, Benchek, Penelope, Benussi, Luisa, Berr, Claudine, Besse, Céline, Bessi, Valentina, Binetti, Giuliano, Bizarro, Alessandra, Blesa, Rafael, Boada, Mercè, Boerwinkle, Eric, Borroni, Barbara, Boschi, Silvia, Bossù, Paola, Bråthen, Geir, Bressler, Jan, Bresner, Catherine, Brodaty, Henry, Brookes, Keeley J, Brusco, Luis Ignacio, Buiza-Rueda, Dolores, Bûrger, Katharina, Burholt, Vanessa, Bush, William S, Calero, Miguel, Cantwell, Laura B, Chene, Geneviève, Chung, Jaeyoon, Cuccaro, Michael L, Carracedo, Ángel, Cecchetti, Roberta, Cervera-Carles, Laura, Charbonnier, Camille, Chen, Hung-Hsin, Chillotti, Caterina, Ciccone, Simona, Claassen, Jurgen AHR, Clark, Christopher, Conti, Elisa, Corma-Gómez, Anaïs, Costantini, Emanuele, Custodero, Carlo, Daian, Delphine, Dalmasso, Maria Carolina, Daniele, Antonio, Dardiotis, Efthimios, Dartigues, Jean-François, de Deyn, Peter Paul, de Paiva Lopes, Katia, de Witte, Lot D, Debette, Stéphanie, Deckert, Jürgen, and del Ser, Teodoro

Subjects
Biochemistry and Cell Biology, Genetics, Biological Sciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Neurodegenerative, Alzheimer's Disease, Human Genome, Prevention, Aging, Brain Disorders, Acquired Cognitive Impairment, Neurosciences, Genetic Testing, 2.1 Biological and endogenous factors, Aetiology, Neurological, Alzheimer Disease, Cognitive Dysfunction, Genome-Wide Association Study, Humans, tau Proteins, EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

Published
2022

12. Soluble Triggering Receptors Expressed on Myeloid Cells (sTREM) in Acute Ischemic Stroke: A Potential Pathway of sTREM-1 and sTREM-2 Associated with Disease Severity.

Author

Salafia, Greta, Carandina, Angelica, Sacco, Roberto Maria, Ferri, Evelyn, Montano, Nicola, Arosio, Beatrice, and Tobaldini, Eleonora

Subjects
ISCHEMIC stroke, MYELOID cells, CEREBROVASCULAR disease, BRAIN damage
Abstract

In 2022, stroke emerged as the most significant cerebrovascular disorder globally, causing 6.55 million deaths. Microglia, crucial for CNS preservation, can exacerbate brain damage in ischemic stroke by triggering neuroinflammation. This process is mediated by receptors on microglia, triggering receptors expressed on myeloid cells (TREM-1 and TREM-2), which have contrasting roles in neuroinflammation. In this study, we recruited 38 patients within 4.5 h from the onset of ischemic stroke. The degree of severity was evaluated by means of the National Institutes of Health Stroke Scale (NIHSS) at admission (T0) and after one week of ischemic events (TW) and the Modified Rankin Scale (mRS) at three months. The plasma concentration of TREMs (sTREM) was analyzed by next-generation ELISA at T0 and TW. The sTREM-1 concentrations at T0 were associated with mRS, while the sTREM-2 concentrations at T0 were associated with both the NIHSS at T0 and the mRS. A strong correlation between sTREM-1 and sTREM-2 was observed, suggesting a dependent modulation of the levels. This study provides insights into the potential pathway of TREM-1 and TREM-2 as a future biomarker for stratifying high-risk patients with ischemic stroke. [ABSTRACT FROM AUTHOR]

Published
2024
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15. 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
2021
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19. CXCR6, a Newly Defined Biomarker of Tissue-Specific Stem Cell Asymmetric Self-Renewal, Identifies More Aggressive Human Melanoma Cancer Stem Cells

Author

Taghizadeh, Rouzbeh, Noh, Minsoo, Huh, Yang Hoon, Ciusani, Emilio, Sigalotti, Luca, Maio, Michele, Arosio, Beatrice, Nicotra, Maria R., Natali, PierGiorgio, Sherley, James L., and La Porta, Caterina A. M.

Subjects
Quantitative Biology - Subcellular Processes, Quantitative Biology - Tissues and Organs
Abstract

Background: A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma cancer stem cells (CSCs) from mutated tissue-specific stem cells; and the second one is the identification of a more aggressive subpopulation of CSCs in melanoma that are CXCR6+. Conclusions/Significance: The association of a more aggressive tumor phenotype with asymmetric self-renewal phenotype reveals a previously unrecognized aspect of tumor cell physiology. Namely, the retention of some tissue-specific stem cell attributes, like the ability to asymmetrically self-renew, impacts the natural history of human tumor development. Knowledge of this new aspect of tumor development and progression may provide new targets for cancer prevention and treatment.

Published
2013
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23. Transferability of a European-derived Alzheimer’s Disease Genetic Risk Score across Multi-Ancestry Populations

Author

Nicolas, Aude, primary, Grenier-Boley, Benjamin, additional, Sherva, Richard, additional, Kim, Yoontae, additional, Kikuchi, Masataka, additional, de Rojas, Itziar, additional, Dalmasso, Carolina, additional, Zhou, Xiaopu, additional, Guen, Yann Le, additional, Arboleda-Bustos, Carlos E, additional, Camargos Bicalho, Maria Aparecida, additional, Guerchet, Maëlenn, additional, van der Lee, Sven, additional, Goss, Monica, additional, Castillo, Atahualpa, additional, Bellenguez, Céline, additional, Küçükali, Fahri, additional, Satizabal Barrera, Claudia, additional, Fongang, Bernard, additional, yang, Qiong, additional, Peters, Oliver, additional, Schneider, Anja, additional, Dichgans, Martin, additional, Rujescu, Dan, additional, Scherbaum, Norbert, additional, Deckert, Jürgen, additional, Riedel-Heller, Steffi, additional, Hausner, Lucrezia, additional, Molina Porcel, Laura, additional, Düzel, Emrah, additional, Grimmer, Timo, additional, Wiltfang, Jens, additional, Heilmann-Heimbach, Stefanie, additional, Moebus, Susanne, additional, Tegos, Thomas, additional, Scarmeas, Nikolaos, additional, Dols-Icardo, Oriol, additional, Moreno, Fermin, additional, Pérez-Tur, Jordi, additional, Bullido, María J., additional, Pastor, Pau, additional, Sánchez-Valle, Raquel, additional, Álvarez, Victoria, additional, Cao, Han, additional, Ip, Nancy Y., additional, Fu, Amy K. Y., additional, Ip, Fanny C. F., additional, Olivar, Natividad, additional, Muchnik, Carolina, additional, Cuesta, Carolina, additional, Campanelli, Lorenzo, additional, Solis, Patricia, additional, Politis, Daniel Gustavo, additional, Kochen, Silvia, additional, Brusco, Luis Ignacio, additional, Boada, Mercè, additional, García-González, Pablo, additional, Puerta, Raquel, additional, Mir, Pablo, additional, Real, Luis M, additional, Piñol-Ripoll, Gerard, additional, María García-Alberca, Jose, additional, Luís Royo, Jose, additional, Rodriguez-Rodriguez, Eloy, additional, Soininen, Hilkka, additional, Heikkinen, Sami, additional, de Mendonça, Alexandre, additional, Mehrabian, Shima, additional, Traykov, Latchezar, additional, Hort, Jakub, additional, Vyhnalek, Martin, additional, Rasmussen, Katrine Laura, additional, Qvist Thomassen, Jesper, additional, Pijnenburg, Yolande A.L., additional, Holstege, Henne, additional, van Swieten, John, additional, Ramakers, Inez, additional, Verhey, Frans, additional, van der Lugt, Aad, additional, Scheltens, Philip, additional, Ortega-Rojas, Jenny, additional, Concha Mera, Ana Gabriela, additional, Mahecha, Maria F., additional, Pardo, Rodrogo, additional, Arboleda, Gonzalo, additional, Graff, Caroline, additional, Papenberg, Goran, additional, Giedraitis, Vilmantas, additional, Boland, Anne, additional, Deleuze, Jean-François, additional, Armando de Marco, Luiz, additional, Nunes de Moraes, Edgar, additional, de Viana, Bernardo, additional, Túlio Gualberto Cintra, Marco, additional, Grsiwold, Anthony, additional, Forund, Tatiana, additional, Cruchaga, Carlos, additional, Haines, Jonathan, additional, Farrer, Lindsay, additional, DeStefano, Anita, additional, Wijsman, Ellen, additional, Mayeux, Richard, additional, Pericak-Vance, Margaret, additional, Kunkle, Brian, additional, Goate, Alison, additional, Schellenberg, Gerard D., additional, Vardarajan, Badri, additional, Wang, Li-San, additional, Leung, Yuk Yee, additional, Dalgard, Clifton, additional, Nicolas, Gael, additional, Wallon, David, additional, Dufouil, Carole, additional, Pasquier, Florence, additional, Hanon, Olivier, additional, Debette, Stéphanie, additional, Grünblatt, Edna, additional, Popp, Julius, additional, Angel, Bárbara, additional, Golger, Sergio, additional, Victoria Chacon, Maria, additional, Aranguiz, Rafael, additional, Orellana, Paulina, additional, Slachevsky, Andrea, additional, Gonzalez-Billault, Christian, additional, Albala, Cecilia, additional, Fuentes, Patricio, additional, Porter, Tenielle, additional, Laws, Simon M, additional, Sachdev, Perminder, additional, Mather, Karen, additional, Hauger, Richard L., additional, Merritt, Victoria, additional, Panizzon, Matthew, additional, Zhang, Rui, additional, Gaziano, Michael, additional, Ghidoni, Roberta, additional, Galimberti, Daniela, additional, Arosio, Beatrice, additional, Mecocci, Patrizia, additional, Solfrizzi, Vincenzo, additional, Parnetti, Lucilla, additional, Squassina, Alessio, additional, Tremolizzo, Lucio, additional, Borroni, Barbara, additional, Nacmias, Benedetta, additional, Caffarra, Paolo, additional, Seripa, Davide, additional, Rainero, Innocenzo, additional, Daniele, Antonio, additional, Piras, Fabrizio, additional, Miyashita, Akinori, additional, Hara, Norikazu, additional, Ozaki, Kouichi, additional, Niida, Shumpei, additional, Williams, Julie, additional, Masullo, Carlo, additional, Amouyel, Philippe, additional, Preux, Pierre-Marie, additional, Mbelesso, Pascal, additional, Bandzouzi, Bébène, additional, Saykin, Andy, additional, Jessen, Frank, additional, Kehoe, Patrick, additional, Van Duijn, Cornelia, additional, Gim, Jungsoo, additional, Ben Salem, Nesrine, additional, Frikke-Schmidt, Ruth, additional, Cherni, Lofti, additional, Greicius, Michael D., additional, Tsolaki, Magda, additional, Sánchez-Juan, Pascual, additional, Romano Silva, Marco Aurélio, additional, Sleegers, Kristel, additional, Ingelsson, Martin, additional, Dartigues, Jean-François, additional, Seshadri, Sudha, additional, Rossi, Giacomina, additional, Morelli, Laura, additional, Hiltunen, Mikko, additional, Sims, Rebecca, additional, van der Flier, Wiesje, additional, Andreassen, Ole, additional, Arboleda, Humberto, additional, Escott-Price, Valentina, additional, Ruiz, Agustín, additional, Lee, Kun Ho, additional, Ikeuchi, Takeshi, additional, Ramirez, Alfredo, additional, Logue, Mark, additional, and Lambert, Jean-Charles, additional

Published
2023
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24. Altered Extracellular Vesicle miRNA Profile in Prodromal Alzheimer’s Disease

Author

Visconte, Caterina, primary, Fenoglio, Chiara, additional, Serpente, Maria, additional, Muti, Paola, additional, Sacconi, Andrea, additional, Rigoni, Marta, additional, Arighi, Andrea, additional, Borracci, Vittoria, additional, Arcaro, Marina, additional, Arosio, Beatrice, additional, Ferri, Evelyn, additional, Golia, Maria Teresa, additional, Scarpini, Elio, additional, and Galimberti, Daniela, additional

Published
2023
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25. An association study of cyclase‐associated protein 2 and frailty

Author

Pelucchi, Silvia, primary, Macchi, Chiara, additional, D'Andrea, Laura, additional, Rossi, Paolo Dionigi, additional, Speciani, Michela Carola, additional, Stringhi, Ramona, additional, Ruscica, Massimiliano, additional, Arosio, Beatrice, additional, Di Luca, Monica, additional, Cesari, Matteo, additional, Edefonti, Valeria, additional, and Marcello, Elena, additional

Published
2023
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26. Klotho Gene Expression Is Decreased in Peripheral Blood Mononuclear Cells in Patients with Alzheimer’s Disease and Frontotemporal Dementia

Author

Sorrentino, Federica, primary, Fenoglio, Chiara, additional, Sacchi, Luca, additional, Serpente, Maria, additional, Arighi, Andrea, additional, Carandini, Tiziana, additional, Arosio, Beatrice, additional, Ferri, Evelyn, additional, Arcaro, Marina, additional, Visconte, Caterina, additional, Rotondo, Emanuela, additional, Scarpini, Elio, additional, and Galimberti, Daniela, additional

Published
2023
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27. Transcutaneous auricular branch vagal nerve stimulation as a non-invasive add-on therapeutic approach for pain in systemic sclerosis

Author

Bellocchi, Chiara, primary, Carandina, Angelica, additional, Della Torre, Alice, additional, Turzi, Massimiliano, additional, Arosio, Beatrice, additional, Marchini, Maurizio, additional, Vigone, Barbara, additional, Scatà, Costanza, additional, Beretta, Lorenzo, additional, Rodrigues, Gabriel Dias, additional, Tobaldini, Eleonora, additional, and Montano, Nicola, additional

Published
2023
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29. A case of right Alzheimer’s disease

Author

Abbate, Carlo, Trimarchi, Pietro D., Inglese, Silvia, Damanti, Sarah, Dolci, Giulia A. M., Ciccone, Simona, Rossi, Paolo D., Mari, Daniela, Arosio, Beatrice, and Cesari, Matteo

Published
2019
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32. Genomic history of the Italian population recapitulates key evolutionary dynamics of both Continental and Southern Europeans

Author

Sazzini, Marco, Abondio, Paolo, Sarno, Stefania, Gnecchi-Ruscone, Guido Alberto, Ragno, Matteo, Giuliani, Cristina, De Fanti, Sara, Ojeda-Granados, Claudia, Boattini, Alessio, Marquis, Julien, Valsesia, Armand, Carayol, Jerome, Raymond, Frederic, Pirazzini, Chiara, Marasco, Elena, Ferrarini, Alberto, Xumerle, Luciano, Collino, Sebastiano, Mari, Daniela, Arosio, Beatrice, Monti, Daniela, Passarino, Giuseppe, D’Aquila, Patrizia, Pettener, Davide, Luiselli, Donata, Castellani, Gastone, Delledonne, Massimo, Descombes, Patrick, Franceschi, Claudio, and Garagnani, Paolo

Published
2020
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34. Genetic Associations between Modifiable Risk Factors and Alzheimer Disease

Author

Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Céline, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Küçükali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Jürgen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Düzel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Pérez-Tur, Jordi, Bullido, María J., Pastor, Pau, Sánchez-Valle, Raquel, Álvarez, Victoria, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Piñol-Ripoll, Gerard, García-Alberca, Jose María, Royo, Jose Luís, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, De Mendonça, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-François, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stéphanie, Grünblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustín, Ramirez, Alfredo, Lambert, Jean-Charles, Frikke-Schmidt, Ruth, Epidemiology, Repositório da Universidade de Lisboa, Luo, J, Thomassen, J, Bellenguez, C, Grenier-Boley, B, de Rojas, I, Castillo, A, Parveen, K, Küçükali, F, Nicolas, A, Peters, O, Schneider, A, Dichgans, M, Rujescu, D, Scherbaum, N, Jürgen, D, Riedel-Heller, S, Hausner, L, Porcel, L, Düzel, E, Grimmer, T, Wiltfang, J, Heilmann-Heimbach, S, Moebus, S, Tegos, T, Scarmeas, N, Clarimon, J, Moreno, F, Pérez-Tur, J, Bullido, M, Pastor, P, Sánchez-Valle, R, Álvarez, V, Boada, M, García-González, P, Puerta, R, Mir, P, Real, L, Piñol-Ripoll, G, García-Alberca, J, Royo, J, Rodriguez-Rodriguez, E, Soininen, H, Kuulasmaa, T, de Mendonça, A, Mehrabian, S, Hort, J, Vyhnalek, M, van der Lee, S, Graff, C, Papenberg, G, Giedraitis, V, Boland, A, Bacq-Daian, D, Deleuze, J, Nicolas, G, Dufouil, C, Pasquier, F, Hanon, O, Debette, S, Grünblatt, E, Popp, J, Benussi, L, Galimberti, D, Arosio, B, Mecocci, P, Solfrizzi, V, Parnetti, L, Squassina, A, Tremolizzo, L, Borroni, B, Nacmias, B, Sorbi, S, Caffarra, P, Seripa, D, Rainero, I, Daniele, A, Masullo, C, Spalletta, G, Williams, J, Amouyel, P, Jessen, F, Kehoe, P, Magda, T, Rossi, G, Sánchez-Juan, P, Sleegers, K, Ingelsson, M, Andreassen, O, Hiltunen, M, Van Duijn, C, Sims, R, van der Flier, W, Ruiz, A, Ramirez, A, Lambert, J, Frikke-Schmidt, R, Human genetics, Neurology, Amsterdam Neuroscience - Neurodegeneration, VU University medical center, Epidemiology and Data Science, APH - Methodology, and APH - Personalized Medicine

Subjects
MED/26 - NEUROLOGIA, Settore MED/26 - NEUROLOGIA, Alzheimer Disease, Modifiable Risk Factors, Genetic Associations, Medizin, genetics, Alzheimer's disease, risk factors
Abstract

© 2023 European Alzheimer’s & Dementia Biobank Mendelian Randomization (EADB-MR) Collaboration. JAMA Network Open. Open Access: This is an open access article distributed under the terms of the CC-BY License, Importance: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. Objective: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. Design, setting, and participants: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. Exposures: Genetically determined modifiable risk factors. Main outcomes and measures: Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. Results: The EADB-diagnosed cohort included 39 106 participants with clinically diagnosed AD and 401 577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]). Conclusions and relevance: This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation., Dr Frikke-Schmidt was funded by grants from the Lundbeck Foundation (grant No. R278-2018-804), the Danish Heart Foundation, and Innovation Fund Denmark (grant No. 9084-00020B).

Published
2023

37. The Free Triiodothyronine/Free Thyroxine Ratio Is Associated with Frailty in Older Adults: A Longitudinal Multisetting Study

Author

Okoye, Chukwuma, primary, Arosio, Beatrice, additional, Carino, Silvia, additional, Putrino, Luana, additional, Franchi, Riccardo, additional, Rogani, Sara, additional, Cesari, Matteo, additional, Mari, Daniela, additional, Vitale, Giovanni, additional, Malara, Alba, additional, Calsolaro, Valeria, additional, and Monzani, Fabio, additional

Published
2023
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38. Genetic Associations between Modifiable Risk Factors and Alzheimer Disease:[Inkl. correction]

Author

Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Céline, Grenier-Boley, Benjamin, De Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Küçükali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Jürgen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Düzel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Pérez-Tur, Jordi, Bullido, María J., Pastor, Pau, Sánchez-Valle, Raquel, Álvarez, Victoria, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Piñol-Ripoll, Gerard, García-Alberca, Jose María, Royo, Jose Luís, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, De Mendonça, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, Van Der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean François, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stéphanie, Grünblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, Van Der Flier, Wiesje, Ruiz, Agustín, Ramirez, Alfredo, Lambert, Jean Charles, Frikke-Schmidt, Ruth, Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Céline, Grenier-Boley, Benjamin, De Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Küçükali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Jürgen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Düzel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Pérez-Tur, Jordi, Bullido, María J., Pastor, Pau, Sánchez-Valle, Raquel, Álvarez, Victoria, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M., Piñol-Ripoll, Gerard, García-Alberca, Jose María, Royo, Jose Luís, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, De Mendonça, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, Van Der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean François, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stéphanie, Grünblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, Van Der Flier, Wiesje, Ruiz, Agustín, Ramirez, Alfredo, Lambert, Jean Charles, and Frikke-Schmidt, Ruth

Abstract

Importance An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. Objective To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. Design, Setting, and Participants This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. Exposures Genetically determined modifiable risk factors. Main Outcomes and Measures Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. Results The EADB-diagnosed cohort included 39 106 participants with clinically diagnosed AD and 401 577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10–mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimiz, Importance: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. Objective: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. Design, Setting, and Participants: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. Exposures: Genetically determined modifiable risk factors. Main Outcomes and Measures: Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. Results: The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the enti

Published
2023

39. Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Author

Le Guen, Yann, Luo, Guo, Ambati, Aditya, Damotte, Vincent, Jansen, Iris, Yu, Eric, Nicolas, Aude, de Rojasj, Itziar, Leal, Thiago Peixoto, Miyashita, Akinori, Bellenguez, Celine, Lian, Michelle Mulan, Parveen, Kayenat, Morizono, Takashi, Park, Hyeonseul, Grenier-Boley, Benjamin, Naito, Tatsuhiko, Kucukali, Fahri, Talyansky, Seth D., Yogeshwar, Selina Maria, Sempere, Vicente, Satake, Wataru, Alvarez, Victoria, Arosio, Beatrice, Belloy, Michael E., Benussi, Luisa, Boland, Anne, Borroni, Barbara, Bullido, Maria J., Caffarra, Paolo, Clarimon, Jordi, Daniele, Antonio, Darling, Daniel, Debette, Stephanie, Deleuze, Jean-Francois, Dichgans, Martin, Dufouil, Carole, During, Emmanuel, Duzel, Emrah, Galimberti, Daniela, Garcia-Ribas, Guillermo, Maria Garcia-Alberca, Jose, Garcia-Gonzalez, Pablo, Giedraitis, Vilmantas, Goldhardt, Oliver, Graff, Caroline, Grunblatt, Edna, Hanon, Olivier, Hausner, Lucrezia, Heilmann-Heimbach, Stefanie, Holstege, Henne, Hort, Jakub, Jung, Yoo Jin, Jurgen, Deckert, Kern, Silke, Kuulasmaa, Teemu, Lee, Kun Ho, Lin, Ling, Masullo, Carlo, Mecocci, Patrizia, Mehrabian, Shima, de Mendonca, Alexandre, Boada, Merce, Mir, Pablo, Moebus, Susanne, Moreno, Fermin, Nacmias, Benedetta, Nicolas, Gael, Niida, Shumpei, Nordestgaard, Borge G., Papenberg, Goran, Papma, Janne, Parnetti, Lucilla, Pasquier, Florence, Pastor, Pau, Peters, Oliver, Pijnenburg, Yolande A. L., Pinol-Ripoll, Gerard, Popp, Julius, Porcel, Laura Molina, Jordi Perez-Tur, Raquel Puertaj, Rainero, Innocenzo, Ramakers, Inez, Real, Luis M., Riedel-Heller, Steffi, Rodriguez-Rodriguez, Eloy, Ross, Owen A., Royo, Jose Luis, Rujescu, Dan, Scarmeas, Nikolaos, Scheltens, Philip, Scherbaum, Norbert, Schneider, Anja, Seripa, Davide, Skoog, Ingmar, Solfrizzi, Vincenzo, Spalletta, Gianfranco, Squassina, Alessio, van Swieten, John, Sanchez-Valle, Raquel, Tan, Eng-King, Tegos, Thomas, Teunissen, Charlotte, Thomassen, Jesper Qvist, Tremolizzo, Lucio, Vyhnalek, Martin, Verhey, Frans, Waern, Margda, Wiltfang, Jens, Zhangc, Jing, Zetterberg, Henrik, Blennow, Kaj, He, Zihuai, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick G., Andreassen, Ole A., Van Duin, Cornelia, Tsolaki, Magda, Sanchez-Juan, Pascual, Frikke-Schmidt, Ruth, Sleegers, Kristel, Todau, Tatsushi, Zettergren, Anna, Ingelsson, Martin, Okada, Yukinori, Rossi, Giacomina, Hiltunen, Mikko, Gim, Jungsoo, Ozaki, Kouichi, Sims, Rebecca, Foo, Jia Nee, van der Fliere, Wiesje, Ikeuchi, Takeshi, Ramirez, Alfredo, Mata, Ignacio, Ruiz, Agustin, Gan-Or, Ziv, Lambert, Jean-Charles, Greicius, Michael D., Mignot, Emmanuel, Le Guen, Yann, Luo, Guo, Ambati, Aditya, Damotte, Vincent, Jansen, Iris, Yu, Eric, Nicolas, Aude, de Rojasj, Itziar, Leal, Thiago Peixoto, Miyashita, Akinori, Bellenguez, Celine, Lian, Michelle Mulan, Parveen, Kayenat, Morizono, Takashi, Park, Hyeonseul, Grenier-Boley, Benjamin, Naito, Tatsuhiko, Kucukali, Fahri, Talyansky, Seth D., Yogeshwar, Selina Maria, Sempere, Vicente, Satake, Wataru, Alvarez, Victoria, Arosio, Beatrice, Belloy, Michael E., Benussi, Luisa, Boland, Anne, Borroni, Barbara, Bullido, Maria J., Caffarra, Paolo, Clarimon, Jordi, Daniele, Antonio, Darling, Daniel, Debette, Stephanie, Deleuze, Jean-Francois, Dichgans, Martin, Dufouil, Carole, During, Emmanuel, Duzel, Emrah, Galimberti, Daniela, Garcia-Ribas, Guillermo, Maria Garcia-Alberca, Jose, Garcia-Gonzalez, Pablo, Giedraitis, Vilmantas, Goldhardt, Oliver, Graff, Caroline, Grunblatt, Edna, Hanon, Olivier, Hausner, Lucrezia, Heilmann-Heimbach, Stefanie, Holstege, Henne, Hort, Jakub, Jung, Yoo Jin, Jurgen, Deckert, Kern, Silke, Kuulasmaa, Teemu, Lee, Kun Ho, Lin, Ling, Masullo, Carlo, Mecocci, Patrizia, Mehrabian, Shima, de Mendonca, Alexandre, Boada, Merce, Mir, Pablo, Moebus, Susanne, Moreno, Fermin, Nacmias, Benedetta, Nicolas, Gael, Niida, Shumpei, Nordestgaard, Borge G., Papenberg, Goran, Papma, Janne, Parnetti, Lucilla, Pasquier, Florence, Pastor, Pau, Peters, Oliver, Pijnenburg, Yolande A. L., Pinol-Ripoll, Gerard, Popp, Julius, Porcel, Laura Molina, Jordi Perez-Tur, Raquel Puertaj, Rainero, Innocenzo, Ramakers, Inez, Real, Luis M., Riedel-Heller, Steffi, Rodriguez-Rodriguez, Eloy, Ross, Owen A., Royo, Jose Luis, Rujescu, Dan, Scarmeas, Nikolaos, Scheltens, Philip, Scherbaum, Norbert, Schneider, Anja, Seripa, Davide, Skoog, Ingmar, Solfrizzi, Vincenzo, Spalletta, Gianfranco, Squassina, Alessio, van Swieten, John, Sanchez-Valle, Raquel, Tan, Eng-King, Tegos, Thomas, Teunissen, Charlotte, Thomassen, Jesper Qvist, Tremolizzo, Lucio, Vyhnalek, Martin, Verhey, Frans, Waern, Margda, Wiltfang, Jens, Zhangc, Jing, Zetterberg, Henrik, Blennow, Kaj, He, Zihuai, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick G., Andreassen, Ole A., Van Duin, Cornelia, Tsolaki, Magda, Sanchez-Juan, Pascual, Frikke-Schmidt, Ruth, Sleegers, Kristel, Todau, Tatsushi, Zettergren, Anna, Ingelsson, Martin, Okada, Yukinori, Rossi, Giacomina, Hiltunen, Mikko, Gim, Jungsoo, Ozaki, Kouichi, Sims, Rebecca, Foo, Jia Nee, van der Fliere, Wiesje, Ikeuchi, Takeshi, Ramirez, Alfredo, Mata, Ignacio, Ruiz, Agustin, Gan-Or, Ziv, Lambert, Jean-Charles, Greicius, Michael D., and Mignot, Emmanuel

Abstract

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1* 04:07, and intermediary with HLA-DRB1* 04:01 and HLA- DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased A beta 42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.

Published
2023
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40. The Free Triiodothyronine/Free Thyroxine Ratio Is Associated with Frailty in Older Adults: A Longitudinal Multisetting Study

Author

Okoye, C, Arosio, B, Carino, S, Putrino, L, Franchi, R, Rogani, S, Cesari, M, Mari, D, Vitale, G, Malara, A, Calsolaro, V, Monzani, F, Okoye, Chukwuma, Arosio, Beatrice, Carino, Silvia, Putrino, Luana, Franchi, Riccardo, Rogani, Sara, Cesari, Matteo, Mari, Daniela, Vitale, Giovanni, Malara, Alba, Calsolaro, Valeria, Monzani, Fabio, Okoye, C, Arosio, B, Carino, S, Putrino, L, Franchi, R, Rogani, S, Cesari, M, Mari, D, Vitale, G, Malara, A, Calsolaro, V, Monzani, F, Okoye, Chukwuma, Arosio, Beatrice, Carino, Silvia, Putrino, Luana, Franchi, Riccardo, Rogani, Sara, Cesari, Matteo, Mari, Daniela, Vitale, Giovanni, Malara, Alba, Calsolaro, Valeria, and Monzani, Fabio

Abstract

Background: Various models have been proposed to predict frailty, including those based on clinical criteria and phenotypes. However, a simple biomarker associated with frailty has been not yet identified. The aim of this study is to evaluate the relationship between free triiodothyronine (fT3)/free thyroxine (fT4) ratio value and the degree of frailty among three different cohorts of older individuals: (1) acutely ill hospitalized patients, (2) nursing-home (NH) residents, and (3) home-dwelling centenarians.Methods: We performed a secondary analysis of de-identified patient-level data from two prospective observational studies on acutely hospitalized older patients (Geriatric Acute Unit [GAU]), and home-dwelling centenarians (CENT), and a retrospective-prospective observational study on older NH residents. Demographic characteristics, along with a 30-items Frailty Index (FI) and serum thyrotropin, fT3 and fT4 measurements were obtained.Results: Six hundred fifteen individuals (aged 86.4 +/- 8.9 years; 55.1% females) were included in the study, including 298 (48.5%) GAU, 250 (40.6%) NH, and 67 (10.9%) CENT. A significant inverse relationship between fT3/fT4 ratio and FI values was observed (rho(s) = -0.17 [confidence interval; CI: -0.092 to 0.252], p < 0.001), and this was confirmed by logistic multivariate analysis (beta = -0.44, odds ratio [OR]: 0.64 [CI: 0.47-0.87], p < 0.001) (after adjustment for age, sex, and cohorts). Moreover, a progressively decreased mortality risk was associated with rising fT3/fT4 ratio (OR 0.60 [CI: 0.44-0.80] beta = -0.51, p < 0.001].Conclusions: The fT3/fT4 ratio value was inversely correlated with frailty degree and mortality risk in a large cohort of older individuals, including centenarians, regardless of their sex and clinical condition. fT3/fT4 ratio value could represent an easily measured independent biochemical marker of frailty degree in older people.

Published
2023

41. Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease

Author

Luo, J, Thomassen, J, Bellenguez, C, Grenier-Boley, B, de Rojas, I, Castillo, A, Parveen, K, Küçükali, F, Nicolas, A, Peters, O, Schneider, A, Dichgans, M, Rujescu, D, Scherbaum, N, Jürgen, D, Riedel-Heller, S, Hausner, L, Porcel, L, Düzel, E, Grimmer, T, Wiltfang, J, Heilmann-Heimbach, S, Moebus, S, Tegos, T, Scarmeas, N, Clarimon, J, Moreno, F, Pérez-Tur, J, Bullido, M, Pastor, P, Sánchez-Valle, R, Álvarez, V, Boada, M, García-González, P, Puerta, R, Mir, P, Real, L, Piñol-Ripoll, G, García-Alberca, J, Royo, J, Rodriguez-Rodriguez, E, Soininen, H, Kuulasmaa, T, de Mendonça, A, Mehrabian, S, Hort, J, Vyhnalek, M, van der Lee, S, Graff, C, Papenberg, G, Giedraitis, V, Boland, A, Bacq-Daian, D, Deleuze, J, Nicolas, G, Dufouil, C, Pasquier, F, Hanon, O, Debette, S, Grünblatt, E, Popp, J, Benussi, L, Galimberti, D, Arosio, B, Mecocci, P, Solfrizzi, V, Parnetti, L, Squassina, A, Tremolizzo, L, Borroni, B, Nacmias, B, Sorbi, S, Caffarra, P, Seripa, D, Rainero, I, Daniele, A, Masullo, C, Spalletta, G, Williams, J, Amouyel, P, Jessen, F, Kehoe, P, Magda, T, Rossi, G, Sánchez-Juan, P, Sleegers, K, Ingelsson, M, Andreassen, O, Hiltunen, M, Van Duijn, C, Sims, R, van der Flier, W, Ruiz, A, Ramirez, A, Lambert, J, Frikke-Schmidt, R, Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Céline, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Küçükali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Jürgen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Düzel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Pérez-Tur, Jordi, Bullido, María J, Pastor, Pau, Sánchez-Valle, Raquel, Álvarez, Victoria, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M, Piñol-Ripoll, Gerard, García-Alberca, Jose María, Royo, Jose Luís, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, de Mendonça, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-François, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stéphanie, Grünblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A, Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustín, Ramirez, Alfredo, Lambert, Jean-Charles, Frikke-Schmidt, Ruth, Luo, J, Thomassen, J, Bellenguez, C, Grenier-Boley, B, de Rojas, I, Castillo, A, Parveen, K, Küçükali, F, Nicolas, A, Peters, O, Schneider, A, Dichgans, M, Rujescu, D, Scherbaum, N, Jürgen, D, Riedel-Heller, S, Hausner, L, Porcel, L, Düzel, E, Grimmer, T, Wiltfang, J, Heilmann-Heimbach, S, Moebus, S, Tegos, T, Scarmeas, N, Clarimon, J, Moreno, F, Pérez-Tur, J, Bullido, M, Pastor, P, Sánchez-Valle, R, Álvarez, V, Boada, M, García-González, P, Puerta, R, Mir, P, Real, L, Piñol-Ripoll, G, García-Alberca, J, Royo, J, Rodriguez-Rodriguez, E, Soininen, H, Kuulasmaa, T, de Mendonça, A, Mehrabian, S, Hort, J, Vyhnalek, M, van der Lee, S, Graff, C, Papenberg, G, Giedraitis, V, Boland, A, Bacq-Daian, D, Deleuze, J, Nicolas, G, Dufouil, C, Pasquier, F, Hanon, O, Debette, S, Grünblatt, E, Popp, J, Benussi, L, Galimberti, D, Arosio, B, Mecocci, P, Solfrizzi, V, Parnetti, L, Squassina, A, Tremolizzo, L, Borroni, B, Nacmias, B, Sorbi, S, Caffarra, P, Seripa, D, Rainero, I, Daniele, A, Masullo, C, Spalletta, G, Williams, J, Amouyel, P, Jessen, F, Kehoe, P, Magda, T, Rossi, G, Sánchez-Juan, P, Sleegers, K, Ingelsson, M, Andreassen, O, Hiltunen, M, Van Duijn, C, Sims, R, van der Flier, W, Ruiz, A, Ramirez, A, Lambert, J, Frikke-Schmidt, R, Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Céline, Grenier-Boley, Benjamin, de Rojas, Itziar, Castillo, Atahualpa, Parveen, Kayenat, Küçükali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Jürgen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Porcel, Laura Molina, Düzel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimon, Jordi, Moreno, Fermin, Pérez-Tur, Jordi, Bullido, María J, Pastor, Pau, Sánchez-Valle, Raquel, Álvarez, Victoria, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M, Piñol-Ripoll, Gerard, García-Alberca, Jose María, Royo, Jose Luís, Rodriguez-Rodriguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, de Mendonça, Alexandre, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-François, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stéphanie, Grünblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A, Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustín, Ramirez, Alfredo, Lambert, Jean-Charles, and Frikke-Schmidt, Ruth

Abstract

Importance: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. Objective: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. Design, Setting, and Participants: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. Exposures: Genetically determined modifiable risk factors. Main Outcomes and Measures: Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. Results: The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire

Published
2023

42. Sarcopenia and Cognitive Decline in Older Adults: Targeting the Muscle–Brain Axis

Author

Arosio, Beatrice, Calvani, Riccardo, Ferri, Evelyn, José Coelho-Junior, Hélio, Carandina, Angelica, Campanelli, Federica, Ghiglieri, Veronica, Marzetti, Emanuele, Picca, Anna, Riccardo Calvani (ORCID:0000-0001-5472-2365), Federica Campanelli (ORCID:0000-0002-6731-7067), Emanuele Marzetti (ORCID:0000-0001-9567-6983), Arosio, Beatrice, Calvani, Riccardo, Ferri, Evelyn, José Coelho-Junior, Hélio, Carandina, Angelica, Campanelli, Federica, Ghiglieri, Veronica, Marzetti, Emanuele, Picca, Anna, Riccardo Calvani (ORCID:0000-0001-5472-2365), Federica Campanelli (ORCID:0000-0002-6731-7067), and Emanuele Marzetti (ORCID:0000-0001-9567-6983)

Abstract

Declines in physical performance and cognition are commonly observed in older adults. The geroscience paradigm posits that a set of processes and pathways shared among age-associated conditions may also serve as a molecular explanation for the complex pathophysiology of physical frailty, sarcopenia, and cognitive decline. Mitochondrial dysfunction, inflammation, metabolic alterations, declines in cellular stemness, and altered intracellular signaling have been observed in muscle aging. Neurological factors have also been included among the determinants of sarcopenia. Neuromuscular junctions (NMJs) are synapses bridging nervous and skeletal muscle systems with a relevant role in age-related musculoskeletal derangement. Patterns of circulating metabolic and neurotrophic factors have been associated with physical frailty and sarcopenia. These factors are mostly related to disarrangements in protein-to-energy conversion as well as reduced calorie and protein intake to sustain muscle mass. A link between sarcopenia and cognitive decline in older adults has also been described with a possible role for muscle-derived mediators (i.e., myokines) in mediating muscle-brain crosstalk. Herein, we discuss the main molecular mechanisms and factors involved in the muscle-brain axis and their possible implication in cognitive decline in older adults. An overview of current behavioral strategies that allegedly act on the muscle-brain axis is also provided.

Published
2023

43. Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease

Author

European Research Council, Instituto de Salud Carlos III, Pérez-Tur, Jordi [0000-0002-9111-1712], European Alzheimer’s & Dementia Biobank Mendelian Randomization (EADB-MR), Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, Rojas, Itziar de, Castillo, Atahualpa, Parveen, Kayenat, Kucukali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Jurgen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Molina Porcel, Laura, Duzel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimón, Jordi, Moreno, Fermín, Pérez-Tur, Jordi, Bullido, Maria J., Pastor, Pau, Sánchez-Valle, Raquel, Álvarez, Victoria, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis Miguel, Piñol-Ripoll, Gerard, García-Alberca, José María, Royo, José Luis, Rodríguez-Rodríguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, Mendonça, Alexandre de, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Grunblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustín, Ramírez, Alfredo, Lambert, Jean-Charles, Frikke-Schmidt, Ruth, European Research Council, Instituto de Salud Carlos III, Pérez-Tur, Jordi [0000-0002-9111-1712], European Alzheimer’s & Dementia Biobank Mendelian Randomization (EADB-MR), Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, Rojas, Itziar de, Castillo, Atahualpa, Parveen, Kayenat, Kucukali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Jurgen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Molina Porcel, Laura, Duzel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimón, Jordi, Moreno, Fermín, Pérez-Tur, Jordi, Bullido, Maria J., Pastor, Pau, Sánchez-Valle, Raquel, Álvarez, Victoria, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis Miguel, Piñol-Ripoll, Gerard, García-Alberca, José María, Royo, José Luis, Rodríguez-Rodríguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, Mendonça, Alexandre de, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Grunblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, van der Flier, Wiesje, Ruiz, Agustín, Ramírez, Alfredo, Lambert, Jean-Charles, and Frikke-Schmidt, Ruth

Abstract

Importance: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. Objective: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. Design, setting, and participants: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. Exposures: Genetically determined modifiable risk factors. Main outcomes and measures: Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. Results: The EADB-diagnosed cohort included 39 106 participants with clinically diagnosed AD and 401 577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK

Published
2023

44. Genetic Associations between Modifiable Risk Factors and Alzheimer Disease

Author

Danish Heart Foundation, Lundbeck Foundation, Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, Rojas, Itziar de, Castillo, Atahualpa, Parveen, Kayenat, Kucukali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Jurgen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Molina Porcel, Laura, Duzel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimón, Jordi, Moreno, Fermín, Pérez-Tur, Jordi, Bullido, Maria J, Pastor, Pau, Sánchez-Valle, Raquel, Álvarez, Victoria, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M, Pinol-Ripoll, Gerard, García-Alberca, José María, Royo, José Luis, Rodríguez-Rodríguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, Mendonça, Alexandre de, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, Van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Grunblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, Van der Flier, Wiesje, Ruiz, Agustin, Ramírez, Alfredo, Lambert, Jean-Charles, Frikke-Schmidt, Ruth, Danish Heart Foundation, Lundbeck Foundation, Luo, Jiao, Thomassen, Jesper Qvist, Bellenguez, Celine, Grenier-Boley, Benjamin, Rojas, Itziar de, Castillo, Atahualpa, Parveen, Kayenat, Kucukali, Fahri, Nicolas, Aude, Peters, Oliver, Schneider, Anja, Dichgans, Martin, Rujescu, Dan, Scherbaum, Norbert, Jurgen, Deckert, Riedel-Heller, Steffi, Hausner, Lucrezia, Molina Porcel, Laura, Duzel, Emrah, Grimmer, Timo, Wiltfang, Jens, Heilmann-Heimbach, Stefanie, Moebus, Susanne, Tegos, Thomas, Scarmeas, Nikolaos, Clarimón, Jordi, Moreno, Fermín, Pérez-Tur, Jordi, Bullido, Maria J, Pastor, Pau, Sánchez-Valle, Raquel, Álvarez, Victoria, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Mir, Pablo, Real, Luis M, Pinol-Ripoll, Gerard, García-Alberca, José María, Royo, José Luis, Rodríguez-Rodríguez, Eloy, Soininen, Hilkka, Kuulasmaa, Teemu, Mendonça, Alexandre de, Mehrabian, Shima, Hort, Jakub, Vyhnalek, Martin, Van der Lee, Sven, Graff, Caroline, Papenberg, Goran, Giedraitis, Vilmantas, Boland, Anne, Bacq-Daian, Delphine, Deleuze, Jean-Francois, Nicolas, Gael, Dufouil, Carole, Pasquier, Florence, Hanon, Olivier, Debette, Stephanie, Grunblatt, Edna, Popp, Julius, Benussi, Luisa, Galimberti, Daniela, Arosio, Beatrice, Mecocci, Patrizia, Solfrizzi, Vincenzo, Parnetti, Lucilla, Squassina, Alessio, Tremolizzo, Lucio, Borroni, Barbara, Nacmias, Benedetta, Sorbi, Sandro, Caffarra, Paolo, Seripa, Davide, Rainero, Innocenzo, Daniele, Antonio, Masullo, Carlo, Spalletta, Gianfranco, Williams, Julie, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick, Magda, Tsolaki, Rossi, Giacomina, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Andreassen, Ole A., Hiltunen, Mikko, Van Duijn, Cornelia, Sims, Rebecca, Van der Flier, Wiesje, Ruiz, Agustin, Ramírez, Alfredo, Lambert, Jean-Charles, and Frikke-Schmidt, Ruth

Abstract

Importance: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia. Objective: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention. Design, Setting, and Participants: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022. Exposures: Genetically determined modifiable risk factors. Main Outcomes and Measures: Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors. Results: The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK B

Published
2023

45. Diencephalic versus Hippocampal Amnesia in Alzheimer’s Disease: The Possible Confabulation-Misidentification Phenotype

Author

Abbate, Carlo, primary, Trimarchi, Pietro D., additional, Fumagalli, Giorgio G., additional, Gallucci, Alessia, additional, Tomasini, Emanuele, additional, Fracchia, Stefania, additional, Rebecchi, Isabella, additional, Morello, Elisabetta, additional, Fontanella, Anna, additional, Parisi, Paola M.R., additional, Tartarone, Federica, additional, Giunco, Fabrizio, additional, Ciccone, Simona, additional, Nicolini, Paola, additional, Lucchi, Tiziano, additional, Arosio, Beatrice, additional, Inglese, Silvia, additional, and Rossi, Paolo D., additional

Published
2023
Full Text
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48. Protective association of HLA‐DRB1*04 subtypes in neurodegenerative diseases implicates acetylated tau PHF6 sequences

Author

Guen, Yann Le, primary, Luo, Guo, additional, Ambati, Aditya, additional, Damotte, Vincent, additional, Jansen, Iris E, additional, Yu, Eric, additional, Nicolas, Aude, additional, de Rojas, Itziar, additional, Leal, Thiago Peixoto, additional, Miyashita, Akinori, additional, Bellenguez, Céline, additional, Lian, Michelle Mulan, additional, Parveen, Kayenat, additional, Morizono, Takashi, additional, Park, Hyeonseul, additional, Grenier‐Boley, Benjamin, additional, Naito, Tatsuhiko, additional, Küçükali, Fahri, additional, Talyansky, Seth D., additional, Yogeshwar, Selina Marie, additional, Sempere, Vicente, additional, Satake, Wataru, additional, Álvarez‐Martínez, Victoria, additional, Arosio, Beatrice, additional, Belloy, Michael E, additional, Benussi, Luisa, additional, Boland, Anne, additional, Borroni, Barbara, additional, Bullido, María J., additional, Caffarra, Paolo, additional, Clarimon, Jordi, additional, Daniele, Antonio, additional, Darling, Daniel, additional, Debette, Stéphanie, additional, Deleuze, Jean‐François, additional, Dichgans, Martin, additional, Dufouil, Carole, additional, During, Emmanuel, additional, Duzel, Emrah, additional, Galimberti, Daniela, additional, García‐Ribas, Guillermo, additional, García‐Alberca, Jose María, additional, García‐González, Pablo, additional, Giedraitis, Vilmantas, additional, Goldhardt, Oliver, additional, Graff, Caroline, additional, Grunblatt, Edna, additional, Hanon, Olivier, additional, Hausner, Lucrezia, additional, Heilmann‐Heimbach, Stefanie, additional, Holstege, Henne, additional, Hort, Jakub, additional, Jung, Yoo Jin, additional, Jurgen, Deckert, additional, Kern, Silke, additional, Kuulasmaa, Teemu, additional, Lee, Kun Ho, additional, Ling, Ling, additional, Masullo, Carlo, additional, Mecocci, Patrizia, additional, Mehrabian, Shima, additional, de Mendonça, Alexandre, additional, Boada, Mercè, additional, Mir, Pablo, additional, Moebus, Susanne, additional, Moreno, Fermin, additional, Nacmias, Benedetta, additional, Nicolas, Gaël, additional, Niida, Shumpei, additional, Nordestgaard, Børge G., additional, Papenberg, Goran, additional, Papma, Janne M., additional, Parnetti, Lucilla, additional, Pasquier, Florence, additional, Pastor, Pau, additional, Peters, Oliver, additional, Pijnenburg, Yolande A.L., additional, Piñol‐Ripoll, Gerard, additional, Popp, Julius, additional, Molina, Laura, additional, Puerta, Raquel, additional, Pérez‐Tur, Jordi, additional, Rainero, Innocenzo, additional, Real, Luis Miguel, additional, Riedel‐Heller, Steffi G., additional, Rodríguez, Eloy Rodríguez, additional, Royo, José Luís, additional, Rujescu, Dan, additional, Scarmeas, Nikolaos, additional, Scheltens, Philip, additional, Scherbaum, Norbert, additional, Schneider, Anja, additional, Seripa, Davide, additional, Skoog, Ingmar, additional, Solfrizzi, Vincenzo, additional, Spalletta, Gianfranco, additional, Squassina, Alessio, additional, van Swieten, John C, additional, Sanchez‐Valle, Raquel, additional, Tan, Eng‐King, additional, Tegos, Thomas, additional, Teunissen, Charlotte E., additional, Thomassen, Jesper Qvist, additional, Tremolizzo, Lucio, additional, Vyhnalek, Martin, additional, Verhey, Frans R.J., additional, Waern, Margda, additional, Wiltfang, Jens, additional, Zhang, Jing, additional, Zetterberg, Henrik, additional, Blennow, Kaj, additional, Williams, Julie, additional, Amouyel, Philippe, additional, Jessen, Frank, additional, Kehoe, Patrick G, additional, Andreassen, Ole, additional, van Duijn, Cornelia M, additional, Tsolaki, Magda, additional, Sanchez‐Juan, Pascual, additional, Frikke‐Schmidt, Ruth, additional, Sleegers, Kristel, additional, Toda, Tatsushi, additional, Zettergren, Anna, additional, Ingelsson, Martin, additional, Okada, Yukinori, additional, Rossi, Giacomina, additional, Hiltunen, Mikko, additional, Gim, Jungsoo, additional, Ozaki, Kouichi, additional, Sims, Rebecca, additional, Foo, Jia Nee, additional, van der Flier, Wiesje M., additional, Ikeuchi, Takeshi, additional, Ramirez, Alfredo, additional, Mata, Ignacio, additional, Ruiz, Agustin, additional, Gan‐Or, Ziv, additional, Lambert, Jean‐Charles, additional, Greicius, Michael D, additional, and Mignot, Emmanuel, additional

Published
2022
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49. Rare missense variant (R251G) on APOE counterbalances the Alzheimer’s disease risk associated with APOE‐ε4

Author

Guen, Yann Le, primary, Belloy, Michael E, additional, Grenier‐Boley, Benjamin, additional, de Rojas, Itziar, additional, Castillo, Atahualpa, additional, Jansen, Iris E, additional, Nicolas, Aude, additional, Bellenguez, Céline, additional, Dalmasso, Carolina, additional, Küçükali, Fahri, additional, Eger, Sarah J, additional, Álvarez‐Martínez, Victoria, additional, Arosio, Beatrice, additional, Benussi, Luisa, additional, Boland, Anne, additional, Borroni, Barbara, additional, Bullido, María J., additional, Caffarra, Paolo, additional, Clarimón, Jordi, additional, Daian, Delphine, additional, Daniele, Antonio, additional, Debette, Stéphanie, additional, Deleuze, Jean‐François, additional, Dichgans, Martin, additional, Dufouil, Carole, additional, Duzel, Emrah, additional, Galimberti, Daniela, additional, García‐Alberca, Jose María, additional, García‐González, Pablo, additional, Giedraitis, Vilmantas, additional, Grimmer, Timo, additional, Graff, Caroline, additional, Grunblatt, Edna, additional, Hanon, Olivier, additional, Hausner, Lucrezia, additional, Heilmann‐Heimbach, Stefanie, additional, Holstege, Henne, additional, Hort, Jakub, additional, Jurgen, Deckert, additional, Kuulasmaa, Teemu, additional, van der Lugt, Aad, additional, Masullo, Carlo, additional, Mecocci, Patrizia, additional, Mehrabian, Shima, additional, de Mendonça, Alexandre, additional, Boada, Mercè, additional, Mir, Pablo, additional, Moebus, Susanne, additional, Moreno, Fermin, additional, Nacmias, Benedetta, additional, Nicolas, Gaël, additional, Papenberg, Goran, additional, Parnetti, Lucilla, additional, Pasquier, Florence, additional, Pastor, Pau, additional, Peters, Oliver, additional, Pijnenburg, Yolande A.L., additional, Piñol‐Ripoll, Gerard, additional, Popp, Julius, additional, Molina, Laura, additional, Puerta, Raquel, additional, Pérez‐Tur, Jordi, additional, Rainero, Innocenzo, additional, Ramakers, Inez H.G.B., additional, Rasmussen, Katrine Laura, additional, Real, Luis Miguel, additional, Riedel‐Heller, Steffi G., additional, Rodríguez, Eloy Rodríguez, additional, Royo, José Luís, additional, Rujescu, Dan, additional, Scarmeas, Nikolaos, additional, Scheltens, Philip, additional, Scherbaum, Norbert, additional, Schneider, Anja, additional, Seripa, Davide, additional, Soininen, Hilkka, additional, Solfrizzi, Vincenzo, additional, Spalletta, Gianfranco, additional, Squassina, Alessio, additional, van Swieten, John C, additional, Sanchez‐Valle, Raquel, additional, Tegos, Thomas, additional, Thomassen, Jesper Qvist, additional, Tremolizzo, Lucio, additional, Verhey, Frans R.J., additional, Vyhnalek, Martin, additional, Wiltfang, Jens, additional, He, Zihuai, additional, Napolioni, Valerio, additional, Amouyel, Philippe, additional, Jessen, Frank, additional, Kehoe, Patrick G, additional, van Duijn, Cornelia M, additional, Tsolaki, Magda, additional, Sanchez‐Juan, Pascual, additional, Sleegers, Kristel, additional, Ingelsson, Martin, additional, Rossi, Giacomina, additional, Hiltunen, Mikko, additional, Sims, Rebecca, additional, van der Flier, Wiesje M., additional, Ramirez, Alfredo, additional, Andreassen, Ole, additional, Frikke‐Schmidt, Ruth, additional, Williams, Julie, additional, Ruiz, Agustin, additional, Lambert, Jean‐Charles, additional, and Greicius, Michael D, additional

Published
2022
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