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1. Future perspective and clinical applicability of the combined use of plasma phosphorylated tau 181 and neurofilament light chain in Subjective Cognitive Decline and Mild Cognitive Impairment

Author

Giacomucci, Giulia, Mazzeo, Salvatore, Ingannato, Assunta, Crucitti, Chiara, Bagnoli, Silvia, Padiglioni, Sonia, Romano, Lucrezia, Galdo, Giulia, Emiliani, Filippo, Frigerio, Daniele, Ferrari, Camilla, Moschini, Valentina, Morinelli, Carmen, Notarelli, Antonella, Sorbi, Sandro, Nacmias, Benedetta, and Bessi, Valentina

Published
2024
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2. A systematic review of progranulin concentrations in biofluids in over 7,000 people—assessing the pathogenicity of GRN mutations and other influencing factors

Author

Swift, Imogen J., Rademakers, Rosa, Finch, NiCole, Baker, Matt, Ghidoni, Roberta, Benussi, Luisa, Binetti, Giuliano, Rossi, Giacomina, Synofzik, Matthis, Wilke, Carlo, Mengel, David, Graff, Caroline, Takada, Leonel T., Sánchez-Valle, Raquel, Antonell, Anna, Galimberti, Daniela, Fenoglio, Chiara, Serpente, Maria, Arcaro, Marina, Schreiber, Stefanie, Vielhaber, Stefan, Arndt, Philipp, Santana, Isabel, Almeida, Maria Rosario, Moreno, Fermín, Barandiaran, Myriam, Gabilondo, Alazne, Stubert, Johannes, Gómez-Tortosa, Estrella, Agüero, Pablo, Sainz, M. José, Gohda, Tomohito, Murakoshi, Maki, Kamei, Nozomu, Kittel-Schneider, Sarah, Reif, Andreas, Weigl, Johannes, Jian, Jinlong, Liu, Chuanju, Serrero, Ginette, Greither, Thomas, Theil, Gerit, Lohmann, Ebba, Gazzina, Stefano, Bagnoli, Silvia, Coppola, Giovanni, Bruni, Amalia, Quante, Mirja, Kiess, Wieland, Hiemisch, Andreas, Jurkutat, Anne, Block, Matthew S., Carlson, Aaron M., Bråthen, Geir, Sando, Sigrid Botne, Grøntvedt, Gøril Rolfseng, Lauridsen, Camilla, Heslegrave, Amanda, Heller, Carolin, Abel, Emily, Gómez-Núñez, Alba, Puey, Roger, Arighi, Andrea, Rotondo, Enmanuela, Jiskoot, Lize C., Meeter, Lieke H. H., Durães, João, Lima, Marisa, Tábuas-Pereira, Miguel, Lemos, João, Boeve, Bradley, Petersen, Ronald C., Dickson, Dennis W., Graff-Radford, Neill R., LeBer, Isabelle, Sellami, Leila, Lamari, Foudil, Clot, Fabienne, Borroni, Barbara, Cantoni, Valentina, Rivolta, Jasmine, Lleó, Alberto, Fortea, Juan, Alcolea, Daniel, Illán-Gala, Ignacio, Andres-Cerezo, Lucie, Van Damme, Philip, Clarimon, Jordi, Steinacker, Petra, Feneberg, Emily, Otto, Markus, van der Ende, Emma L., van Swieten, John C., Seelaar, Harro, Zetterberg, Henrik, Sogorb-Esteve, Aitana, and Rohrer, Jonathan D.

Published
2024
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4. PRedicting the EVolution of SubjectIvE Cognitive Decline to Alzheimer’s Disease With machine learning: the PREVIEW study protocol

Author

Mazzeo, Salvatore, Lassi, Michael, Padiglioni, Sonia, Vergani, Alberto Arturo, Moschini, Valentina, Scarpino, Maenia, Giacomucci, Giulia, Burali, Rachele, Morinelli, Carmen, Fabbiani, Carlo, Galdo, Giulia, Amato, Lorenzo Gaetano, Bagnoli, Silvia, Emiliani, Filippo, Ingannato, Assunta, Nacmias, Benedetta, Sorbi, Sandro, Grippo, Antonello, Mazzoni, Alberto, and Bessi, Valentina

Published
2023
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5. Gene Expression Imputation Across Multiple Tissue Types Provides Insight Into the Genetic Architecture of Frontotemporal Dementia and Its Clinical Subtypes

Author

Reus, Lianne M, Pasaniuc, Bogdan, Posthuma, Danielle, Boltz, Toni, Consortium, International FTD-Genomics, Ferrari, Raffaele, Hernandez, Dena G, Nalls, Michael A, Rohrer, Jonathan D, Ramasamy, Adaikalavan, Kwok, John BJ, Dobson-Stone, Carol, Brooks, William S, Schofield, Peter R, Halliday, Glenda M, Hodges, John R, Piguet, Olivier, Bartley, Lauren, Thompson, Elizabeth, Hernández, Isabel, Ruiz, Agustín, Boada, Mercè, Borroni, Barbara, Padovani, Alessandro, Cruchaga, Carlos, Cairns, Nigel J, Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Forloni, Gianluigi, Galimberti, Daniela, Fenoglio, Chiara, Serpente, Maria, Scarpini, Elio, Clarimón, Jordi, Lleó, Alberto, Blesa, Rafael, Waldö, Maria Landqvist, Nilsson, Karin, Nilsson, Christer, Mackenzie, Ian RA, Hsiung, Ging-Yuek R, Mann, David MA, Grafman, Jordan, Morris, Christopher M, Attems, Johannes, Griffiths, Timothy D, McKeith, Ian G, Thomas, Alan J, Pietrini, Pietro, Huey, Edward D, Wassermann, Eric M, Baborie, Atik, Jaros, Evelyn, Tierney, Michael C, Pastor, Pau, Razquin, Cristina, Ortega-Cubero, Sara, Alonso, Elena, Perneczky, Robert, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Kurz, Alexander, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Rogaeva, Ekaterina, St. George-Hyslop, Peter, Rossi, Giacomina, Tagliavini, Fabrizio, Giaccone, Giorgio, Rowe, James B, Schlachetzki, Johannes CM, Uphill, James, Collinge, John, Mead, Simon, Danek, Adrian, Van Deerlin, Vivianna M, Grossman, Murray, Trojanowski, John Q, van der Zee, Julie, Van Broeckhoven, Christine, Cappa, Stefano F, Le Ber, Isabelle, Hannequin, Didier, Golfier, Véronique, Vercelletto, Martine, Brice, Alexis, Nacmias, Benedetta, Sorbi, Sandro, Bagnoli, Silvia, Piaceri, Irene, Nielsen, Jørgen E, Hjermind, Lena E, Riemenschneider, Matthias, Mayhaus, Manuel, Ibach, Bernd, Gasparoni, Gilles, Pichler, Sabrina, and Gu, Wei

Subjects
Biological Sciences, Genetics, Frontotemporal Dementia (FTD), Neurodegenerative, Human Genome, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease Related Dementias (ADRD), Rare Diseases, Acquired Cognitive Impairment, Brain Disorders, Dementia, Aging, Biotechnology, Neurosciences, 2.1 Biological and endogenous factors, Neurological, Frontotemporal Dementia, Gene Expression, Humans, International FTD-Genomics Consortium, 17q21.31 inversion region, Dorsolateral prefrontal cortex, Expression quantitative trait loci, Frontotemporal dementia, SEC22B, Transcriptome-wide association study, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences, Psychology
Abstract

BackgroundThe etiology of frontotemporal dementia (FTD) is poorly understood. To identify genes with predicted expression levels associated with FTD, we integrated summary statistics with external reference gene expression data using a transcriptome-wide association study approach.MethodsFUSION software was used to leverage FTD summary statistics (all FTD: n = 2154 cases, n = 4308 controls; behavioral variant FTD: n = 1337 cases, n = 2754 controls; semantic dementia: n = 308 cases, n = 616 controls; progressive nonfluent aphasia: n = 269 cases, n = 538 controls; FTD with motor neuron disease: n = 200 cases, n = 400 controls) from the International FTD-Genomics Consortium with 53 expression quantitative loci tissue type panels (n = 12,205; 5 consortia). Significance was assessed using a 5% false discovery rate threshold.ResultsWe identified 73 significant gene-tissue associations for FTD, representing 44 unique genes in 34 tissue types. Most significant findings were derived from dorsolateral prefrontal cortex splicing data (n = 19 genes, 26%). The 17q21.31 inversion locus contained 23 significant associations, representing 6 unique genes. Other top hits included SEC22B (a gene involved in vesicle trafficking), TRGV5, and ZNF302. A single gene finding (RAB38) was observed for behavioral variant FTD. For other clinical subtypes, no significant associations were observed.ConclusionsWe identified novel candidate genes (e.g., SEC22B) and previously reported risk regions (e.g., 17q21.31) for FTD. Most significant associations were observed in dorsolateral prefrontal cortex splicing data despite the modest sample size of this reference panel. This suggests that our findings are specific to FTD and are likely to be biologically relevant highlights of genes at different FTD risk loci that are contributing to the disease pathology.

Published
2021

6. C9orf72, age at onset, and ancestry help discriminate behavioral from language variants in FTLD cohorts

Author

Costa, Beatrice, Manzoni, Claudia, Bernal-Quiros, Manuel, Kia, Demis A, Aguilar, Miquel, Alvarez, Ignacio, Alvarez, Victoria, Andreassen, Ole, Anfossi, Maria, Bagnoli, Silvia, Benussi, Luisa, Bernardi, Livia, Binetti, Giuliano, Blackburn, Daniel, Boada, Mercè, Borroni, Barbara, Bowns, Lucy, Bråthen, Geir, Bruni, Amalia C, Chiang, Huei-Hsin, Clarimon, Jordi, Colville, Shuna, Conidi, Maria E, Cope, Tom E, Cruchaga, Carlos, Cupidi, Chiara, Di Battista, Maria Elena, Diehl-Schmid, Janine, Diez-Fairen, Monica, Dols-Icardo, Oriol, Durante, Elisabetta, Flisar, Dušan, Frangipane, Francesca, Galimberti, Daniela, Gallo, Maura, Gallucci, Maurizio, Ghidoni, Roberta, Graff, Caroline, Grafman, Jordan H, Grossman, Murray, Hardy, John, Hernández, Isabel, Holloway, Guy JT, Huey, Edward D, Illán-Gala, Ignacio, Karydas, Anna, Khoshnood, Behzad, Kramberger, Milica G, Kristiansen, Mark, Lewis, Patrick A, Lleó, Alberto, Madhan, Gaganjit K, Maletta, Raffaele, Maver, Aleš, Menendez-Gonzalez, Manuel, Milan, Graziella, Miller, Bruce, Mol, Merel O, Momeni, Parastoo, Moreno-Grau, Sonia, Morris, Chris M, Nacmias, Benedetta, Nilsson, Christer, Novelli, Valeria, Öijerstedt, Linn, Padovani, Alessandro, Pal, Suvankar, Panchbhaya, Yasmin, Pastor, Pau, Peterlin, Borut, Piaceri, Irene, Pickering-Brown, Stuart, Pijnenburg, Yolande AL, Puca, Annibale A, Rainero, Innocenzo, Rendina, Antonella, Richardson, Anna MT, Rogaeva, Ekaterina, Rogelj, Boris, Rollinson, Sara, Rossi, Giacomina, Rossmeier, Carola, Rowe, James B, Rubino, Elisa, Ruiz, Agustín, Sanchez-Valle, Raquel, Sando, Sigrid B, Santillo, Alexander F, Saxon, Jennifer, Scarpini, Elio, Serpente, Maria, Smirne, Nicoletta, Sorbi, Sandro, Suh, EunRan, Tagliavini, Fabrizio, Thompson, Jennifer C, Trojanowski, John Q, Van Deerlin, Vivianna M, Van der Zee, Julie, and Van Broeckhoven, Christine

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Rare Diseases, Acquired Cognitive Impairment, Alzheimer's Disease Related Dementias (ADRD), Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Frontotemporal Dementia (FTD), Genetics, Clinical Research, Dementia, Neurological, Age of Onset, Aged, Aged, 80 and over, Aphasia, Primary Progressive, C9orf72 Protein, Cohort Studies, DNA Repeat Expansion, Europe, Female, Frontotemporal Dementia, Frontotemporal Lobar Degeneration, Geography, Humans, Male, Mediterranean Region, Middle Aged, Principal Component Analysis, Scandinavian and Nordic Countries, Syndrome, International FTD-Genetics Consortium, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveWe sought to characterize C9orf72 expansions in relation to genetic ancestry and age at onset (AAO) and to use these measures to discriminate the behavioral from the language variant syndrome in a large pan-European cohort of frontotemporal lobar degeneration (FTLD) cases.MethodsWe evaluated expansions frequency in the entire cohort (n = 1,396; behavioral variant frontotemporal dementia [bvFTD] [n = 800], primary progressive aphasia [PPA] [n = 495], and FTLD-motor neuron disease [MND] [n = 101]). We then focused on the bvFTD and PPA cases and tested for association between expansion status, syndromes, genetic ancestry, and AAO applying statistical tests comprising Fisher exact tests, analysis of variance with Tukey post hoc tests, and logistic and nonlinear mixed-effects model regressions.ResultsWe found C9orf72 pathogenic expansions in 4% of all cases (56/1,396). Expansion carriers differently distributed across syndromes: 12/101 FTLD-MND (11.9%), 40/800 bvFTD (5%), and 4/495 PPA (0.8%). While addressing population substructure through principal components analysis (PCA), we defined 2 patients groups with Central/Northern (n = 873) and Southern European (n = 523) ancestry. The proportion of expansion carriers was significantly higher in bvFTD compared to PPA (5% vs 0.8% [p = 2.17 × 10-5; odds ratio (OR) 6.4; confidence interval (CI) 2.31-24.99]), as well as in individuals with Central/Northern European compared to Southern European ancestry (4.4% vs 1.8% [p = 1.1 × 10-2; OR 2.5; CI 1.17-5.99]). Pathogenic expansions and Central/Northern European ancestry independently and inversely correlated with AAO. Our prediction model (based on expansions status, genetic ancestry, and AAO) predicted a diagnosis of bvFTD with 64% accuracy.ConclusionsOur results indicate correlation between pathogenic C9orf72 expansions, AAO, PCA-based Central/Northern European ancestry, and a diagnosis of bvFTD, implying complex genetic risk architectures differently underpinning the behavioral and language variant syndromes.

Published
2020

7. Degradation of EEG microstates patterns in subjective cognitive decline and mild cognitive impairment: Early biomarkers along the Alzheimer’s Disease continuum?

Author

Lassi, Michael, Fabbiani, Carlo, Mazzeo, Salvatore, Burali, Rachele, Vergani, Alberto Arturo, Giacomucci, Giulia, Moschini, Valentina, Morinelli, Carmen, Emiliani, Filippo, Scarpino, Maenia, Bagnoli, Silvia, Ingannato, Assunta, Nacmias, Benedetta, Padiglioni, Sonia, Micera, Silvestro, Sorbi, Sandro, Grippo, Antonello, Bessi, Valentina, and Mazzoni, Alberto

Published
2023
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8. Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study

Author

Pottier, Cyril, Zhou, Xiaolai, Perkerson, Ralph B, Baker, Matt, Jenkins, Gregory D, Serie, Daniel J, Ghidoni, Roberta, Benussi, Luisa, Binetti, Giuliano, de Munain, Adolfo López, Zulaica, Miren, Moreno, Fermin, Le Ber, Isabelle, Pasquier, Florence, Hannequin, Didier, Sánchez-Valle, Raquel, Antonell, Anna, Lladó, Albert, Parsons, Tammee M, Finch, NiCole A, Finger, Elizabeth C, Lippa, Carol F, Huey, Edward D, Neumann, Manuela, Heutink, Peter, Synofzik, Matthis, Wilke, Carlo, Rissman, Robert A, Slawek, Jaroslaw, Sitek, Emilia, Johannsen, Peter, Nielsen, Jørgen E, Ren, Yingxue, van Blitterswijk, Marka, DeJesus-Hernandez, Mariely, Christopher, Elizabeth, Murray, Melissa E, Bieniek, Kevin F, Evers, Bret M, Ferrari, Camilla, Rollinson, Sara, Richardson, Anna, Scarpini, Elio, Fumagalli, Giorgio G, Padovani, Alessandro, Hardy, John, Momeni, Parastoo, Ferrari, Raffaele, Frangipane, Francesca, Maletta, Raffaele, Anfossi, Maria, Gallo, Maura, Petrucelli, Leonard, Suh, EunRan, Lopez, Oscar L, Wong, Tsz H, van Rooij, Jeroen GJ, Seelaar, Harro, Mead, Simon, Caselli, Richard J, Reiman, Eric M, Sabbagh, Marwan Noel, Kjolby, Mads, Nykjaer, Anders, Karydas, Anna M, Boxer, Adam L, Grinberg, Lea T, Grafman, Jordan, Spina, Salvatore, Oblak, Adrian, Mesulam, M-Marsel, Weintraub, Sandra, Geula, Changiz, Hodges, John R, Piguet, Olivier, Brooks, William S, Irwin, David J, Trojanowski, John Q, Lee, Edward B, Josephs, Keith A, Parisi, Joseph E, Ertekin-Taner, Nilüfer, Knopman, David S, Nacmias, Benedetta, Piaceri, Irene, Bagnoli, Silvia, Sorbi, Sandro, Gearing, Marla, Glass, Jonathan, Beach, Thomas G, Black, Sandra E, Masellis, Mario, Rogaeva, Ekaterina, Vonsattel, Jean-Paul, Honig, Lawrence S, Kofler, Julia, Bruni, Amalia C, Snowden, Julie, Mann, David, and Pickering-Brown, Stuart

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Frontotemporal Dementia (FTD), Neurodegenerative, Dementia, Genetics, Aging, Prevention, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Alzheimer's Disease Related Dementias (ADRD), Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Aetiology, Neurological, Age of Onset, Aged, Case-Control Studies, Cerebellum, Female, Frontotemporal Lobar Degeneration, Genetic Predisposition to Disease, Genome-Wide Association Study, Glial Cell Line-Derived Neurotrophic Factor Receptors, Humans, Male, Middle Aged, Mutation, Progranulins, RNA, Messenger, Neurology & Neurosurgery, Clinical sciences
Abstract

BackgroundLoss-of-function mutations in GRN cause frontotemporal lobar degeneration (FTLD). Patients with GRN mutations present with a uniform subtype of TAR DNA-binding protein 43 (TDP-43) pathology at autopsy (FTLD-TDP type A); however, age at onset and clinical presentation are variable, even within families. We aimed to identify potential genetic modifiers of disease onset and disease risk in GRN mutation carriers.MethodsThe study was done in three stages: a discovery stage, a replication stage, and a meta-analysis of the discovery and replication data. In the discovery stage, genome-wide logistic and linear regression analyses were done to test the association of genetic variants with disease risk (case or control status) and age at onset in patients with a GRN mutation and controls free of neurodegenerative disorders. Suggestive loci (p

Published
2018

10. Human iPSC-Derived Hippocampal Spheroids: An Innovative Tool for Stratifying Alzheimer Disease Patient-Specific Cellular Phenotypes and Developing Therapies

Author

Pomeshchik, Yuriy, Klementieva, Oxana, Gil, Jeovanis, Martinsson, Isak, Hansen, Marita Grønning, de Vries, Tessa, Sancho-Balsells, Anna, Russ, Kaspar, Savchenko, Ekaterina, Collin, Anna, Vaz, Ana Rita, Bagnoli, Silvia, Nacmias, Benedetta, Rampon, Claire, Sorbi, Sandro, Brites, Dora, Marko-Varga, György, Kokaia, Zaal, Rezeli, Melinda, Gouras, Gunnar K., and Roybon, Laurent

Published
2020
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11. Putative novel CSF biomarkers of Alzheimer’s disease based on the novel concept of generic protein misfolding and proteotoxicity: the PRAMA cohort

Author

Bigi, Alessandra, primary, Fani, Giulia, additional, Bessi, Valentina, additional, Napolitano, Liliana, additional, Bagnoli, Silvia, additional, Ingannato, Assunta, additional, Neri, Lorenzo, additional, Cascella, Roberta, additional, Matteini, Paolo, additional, Sorbi, Sandro, additional, Nacmias, Benedetta, additional, Cecchi, Cristina, additional, and Chiti, Fabrizio, additional

Published
2024
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12. Distribution of the C9orf72 hexanucleotide repeat expansion in healthy subjects: a multicenter study promoted by the Italian IRCCS network of neuroscience and neurorehabilitation

Author

Giardina, Emiliano, primary, Mandich, Paola, additional, Ghidoni, Roberta, additional, Ticozzi, Nicola, additional, Rossi, Giacomina, additional, Fenoglio, Chiara, additional, Tiziano, Francesco Danilo, additional, Esposito, Federica, additional, Capellari, Sabina, additional, Nacmias, Benedetta, additional, Mineri, Rossana, additional, Campopiano, Rosa, additional, Di Pilla, Luana, additional, Sammarone, Federica, additional, Zampatti, Stefania, additional, Peconi, Cristina, additional, De Angelis, Flavio, additional, Palmieri, Ilaria, additional, Galandra, Caterina, additional, Nicodemo, Eleonora, additional, Origone, Paola, additional, Gotta, Fabio, additional, Ponti, Clarissa, additional, Nicsanu, Roland, additional, Benussi, Luisa, additional, Peverelli, Silvia, additional, Ratti, Antonia, additional, Ricci, Martina, additional, Di Fede, Giuseppe, additional, Magri, Stefania, additional, Serpente, Maria, additional, Lattante, Serena, additional, Domi, Teuta, additional, Carrera, Paola, additional, Saltimbanco, Elisa, additional, Bagnoli, Silvia, additional, Ingannato, Assunta, additional, Albanese, Alberto, additional, Tagliavini, Fabrizio, additional, Lodi, Raffaele, additional, Caltagirone, Carlo, additional, Gambardella, Stefano, additional, Valente, Enza Maria, additional, and Silani, Vincenzo, additional

Published
2024
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13. Frontotemporal dementia and its subtypes: a genome-wide association study

Author

Ferrari, Raffaele, Hernandez, Dena G, Nalls, Michael A, Rohrer, Jonathan D, Ramasamy, Adaikalavan, Kwok, John BJ, Dobson-Stone, Carol, Brooks, William S, Schofield, Peter R, Halliday, Glenda M, Hodges, John R, Piguet, Olivier, Bartley, Lauren, Thompson, Elizabeth, Haan, Eric, Hernández, Isabel, Ruiz, Agustín, Boada, Mercè, Borroni, Barbara, Padovani, Alessandro, Cruchaga, Carlos, Cairns, Nigel J, Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Forloni, Gianluigi, Galimberti, Daniela, Fenoglio, Chiara, Serpente, Maria, Scarpini, Elio, Clarimón, Jordi, Lleó, Alberto, Blesa, Rafael, Waldö, Maria Landqvist, Nilsson, Karin, Nilsson, Christer, Mackenzie, Ian RA, Hsiung, Ging-Yuek R, Mann, David MA, Grafman, Jordan, Morris, Christopher M, Attems, Johannes, Griffiths, Timothy D, McKeith, Ian G, Thomas, Alan J, Pietrini, P, Huey, Edward D, Wassermann, Eric M, Baborie, Atik, Jaros, Evelyn, Tierney, Michael C, Pastor, Pau, Razquin, Cristina, Ortega-Cubero, Sara, Alonso, Elena, Perneczky, Robert, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Kurz, Alexander, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Rogaeva, Ekaterina, St George-Hyslop, Peter, Rossi, Giacomina, Tagliavini, Fabrizio, Giaccone, Giorgio, Rowe, James B, Schlachetzki, Johannes CM, Uphill, James, Collinge, John, Mead, Simon, Danek, Adrian, Van Deerlin, Vivianna M, Grossman, Murray, Trojanowski, John Q, van der Zee, Julie, Deschamps, William, Van Langenhove, Tim, Cruts, Marc, Van Broeckhoven, Christine, Cappa, Stefano F, Le Ber, Isabelle, Hannequin, Didier, Golfier, Véronique, Vercelletto, Martine, Brice, Alexis, Nacmias, Benedetta, Sorbi, Sandro, Bagnoli, Silvia, Piaceri, Irene, Nielsen, Jørgen E, Hjermind, Lena E, Riemenschneider, Matthias, Mayhaus, Manuel, Ibach, Bernd, Gasparoni, Gilles, Pichler, Sabrina, Gu, Wei, and Rossor, Martin N

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Dementia, Frontotemporal Dementia (FTD), Brain Disorders, Genetics, Clinical Research, Rare Diseases, Prevention, Acquired Cognitive Impairment, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Alzheimer's Disease Related Dementias (ADRD), Human Genome, Neurodegenerative, 2.1 Biological and endogenous factors, Neurological, Adult, Aged, Aged, 80 and over, Female, Frontotemporal Dementia, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Neurology & Neurosurgery, Clinical sciences
Abstract

BackgroundFrontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72--have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.MethodsWe did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p

Published
2014

15. Plasma neurofilament light chain predicts Alzheimer's disease in patients with subjective cognitive decline and mild cognitive impairment: A cross‐sectional and longitudinal study.

Author

Mazzeo, Salvatore, Ingannato, Assunta, Giacomucci, Giulia, Manganelli, Alberto, Moschini, Valentina, Balestrini, Juri, Cavaliere, Arianna, Morinelli, Carmen, Galdo, Giulia, Emiliani, Filippo, Piazzesi, Diletta, Crucitti, Chiara, Frigerio, Daniele, Polito, Cristina, Berti, Valentina, Bagnoli, Silvia, Padiglioni, Sonia, Sorbi, Sandro, Nacmias, Benedetta, and Bessi, Valentina

Subjects
MILD cognitive impairment, ALZHEIMER'S patients, COGNITION disorders, CYTOPLASMIC filaments, POSITRON emission tomography, ALZHEIMER'S disease
Abstract

Background and purpose: We aimed to evaluate the accuracy of plasma neurofilament light chain (NfL) in predicting Alzheimer's disease (AD) and the progression of cognitive decline in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Methods: This longitudinal cohort study involved 140 patients (45 with SCD, 73 with MCI, and 22 with AD dementia [AD‐D]) who underwent plasma NfL and AD biomarker assessments (cerebrospinal fluid, amyloid positron emission tomography [PET], and 18F‐fluorodeoxyglucose‐PET) at baseline. The patients were rated according to the amyloid/tau/neurodegeneration (A/T/N) system and followed up for a mean time of 2.72 ± 0.95 years to detect progression from SCD to MCI and from MCI to AD. Forty‐eight patients (19 SCD, 29 MCI) also underwent plasma NfL measurements 2 years after baseline. Results: At baseline, plasma NfL detected patients with biomarker profiles consistent with AD (A+/T+/N+ or A+/T+/N−) with high accuracy (area under the curve [AUC] 0.82). We identified cut‐off values of 19.45 pg/mL for SCD and 20.45 pg/mL for MCI. During follow‐up, nine SCD patients progressed to MCI (progressive SCD [p‐SCD]), and 14 MCI patients developed AD dementia (progressive MCI [p‐MCI]). The previously identified cut‐off values provided good accuracy in identifying p‐SCD (80% [95% confidence interval 65.69: 94.31]). The rate of NfL change was higher in p‐MCI (3.52 ± 4.06 pg/mL) compared to non‐progressive SCD (0.81 ± 1.25 pg/mL) and non‐progressive MCI (−0.13 ± 3.24 pg/mL) patients. A rate of change lower than 1.64 pg/mL per year accurately excluded progression from MCI to AD (AUC 0.954). Conclusion: Plasma NfL concentration and change over time may be a reliable, non‐invasive tool to detect AD and the progression of cognitive decline at the earliest stages of the disease. [ABSTRACT FROM AUTHOR]

Published
2024
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16. 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, Antúnez, Carmen, Antonell, Anna, Tankard, Rick M., Bis, Joshua C., Sims, Rebecca, Bellenguez, Céline, Quintela, Inés, González-Perez, Antonio, Calero, Miguel, Macías, Juan, Blesa, Rafael, Cervera-Carles, Laura, Menéndez-González, Manuel, Royo, Jose Luís, Moreno, Fermin, Huerto Vilas, Raquel, Baquero, Miquel, Diez-Fairen, Mónica, Lage, Carmen, García-González, Pablo, Valero, Sergi, Ullgren, Abbe, Naj, Adam C., Lemstra, Afina W., 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, 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, 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., Smith, A. David, Saenz, Aldo, Bizzarro, Alessandra, Lauria, Alessandra, Vacca, Alessandro, Solomon, Alina, Anastasiou, Anna, Richardson, Anna, Boland, Anne, Koivisto, Anne, Daniele, Antonio, Greco, Antonio, Marianthi, Arnaoutoglou, McGuinness, Bernadette, Fin, Bertrand, Ferrari, Camilla, Custodero, Carlo, Ferrarese, Carlo, Ingino, Carlos, Mangone, Carlos, Reyes Toso, Carlos, Martínez, Carmen, Cuesta, Carolina, Muchnik, Carolina, Joachim, Catharine, Ortiz, Cecilia, Besse, Céline, Johansson, Charlotte, Zoia, Chiara Paola, Laske, Christoph, Anastasiou, Costas, Palacio, Dana Lis, Politis, Daniel G., Janowitz, Daniel, Craig, David, Mann, David M., Neary, David, Jürgen, Deckert, Daian, Delphine, Belezhanska, Diyana, Kohler, Eduardo, Castaño, Eduardo M., Koutsouraki, Effrosyni, Chipi, Elena, De Roeck, Ellen, Costantini, Emanuele, Vardy, Emma R. L. C., Piras, Fabrizio, Roveta, Fausto, Piras, Federica, Prestia, Federico Ariel, Assogna, Francesca, Salani, Francesca, Sala, Gessica, Lacidogna, Giordano, Novack, Gisela, Wilcock, Gordon, Thonberg, Håkan, Kölsch, Heike, Weber, Heike, Boecker, Henning, Etchepareborda, Ignacio, Piaceri, Irene, Tuomilehto, Jaakko, Lindström, Jaana, Laczo, Jan, Johnston, Janet, Deleuze, Jean-François, Harris, Jenny, Schott, Jonathan M., Priller, Josef, Bacha, Juan Ignacio, Snowden, Julie, Lisso, Julieta, Mihova, Kalina Yonkova, Traykov, Latchezar, Morelli, Laura, Brusco, Luis Ignacio, Rainer, Malik, Takalo, Mari, Bjerke, Maria, Del Zompo, Maria, Serpente, Maria, Sanchez Abalos, Mariana, Rios, Mario, Peltonen, Markku, Herrman, Martin J., Kohler, Matias, Rojo, Matias, Jones, Matthew, Orsini, Michela, Medel, Nancy, Olivar, Natividad, Fox, Nick C., Salvadori, Nicola, Hooper, Nigel M., Galeano, Pablo, Solis, Patricia, Bastiani, Patrizia, Passmore, Peter, Heun, Reinhard, Antikainen, Riitta, Olaso, Robert, Perneczky, Robert, Germani, Sandra, López-García, Sara, Love, Seth, Mehrabian, Shima, Bagnoli, Silvia, Kochen, Silvia, Andreoni, Simona, Teipel, Stefan, Todd, Stephen, Pickering-Brown, Stuart, Natunen, Teemu, Tegos, Thomas, Laatikainen, Tiina, Strandberg, Timo, Polvikoski, Tuomo M., Matoska, Vaclav, Ciullo, Valentina, Cores, Valeria, Solfrizzi, Vincenzo, Lisetti, Viviana, Sevillano, Zulma, Abdelnour, C., Aguilera, N., Alarcon, E., Alegret, M., Benaque, A., Boada, M., Buendia, M., Cañabate, P., Carracedo, A., de Rojas, I., Diego, S., Espinosa, A., Gailhajenet, A., García-González, P., Gil, S., Guitart, M., González-Pérez, A., 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., 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., Garcia Madrona, S., Gómez-Garre, P., 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., Martín Montes, A., Martínez, B., Martínez, C., Martínez, V., Martínez-Lage Álvarez, P., Medina, M., Mendioroz Iriarte, M., Menéndez-González, 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., Sanchez del Valle Díaz, R., Sánchez-Juan, P., Sastre, I., Vicente, M.P., Vigo-Ortega, R., Vivancos, L., Macleod, C., McCracken, C., Brayne, Carol, Bresner, Catherine, Grozeva, Detelina, Bellou, Eftychia, Sommerville, Ewen W., Matthews, F., Leonenko, Ganna, Menzies, Georgina, Windle, Gill, Harwood, Janet, Phillips, Judith, Bennett, K., Luckuck, Lauren, Clare, Linda, Woods, Robert, Saad, Salha, Burholt, Vanessa, 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, Smith, A David, Saenz, Aldo, Bizzarro, Alessandra, Lauria, Alessandra, Vacca, Alessandro, Solomon, Alina, Anastasiou, Anna, Richardson, Anna, Boland, Anne, Koivisto, Anne, Daniele, Antonio, Greco, Antonio, Marianthi, Arnaoutoglou, McGuinness, Bernadette, Fin, Bertrand, Ferrari, Camilla, Custodero, Carlo, Ferrarese, Carlo, Ingino, Carlos, Mangone, Carlos, Reyes Toso, Carlos, Martínez, Carmen, Cuesta, Carolina, Muchnik, Carolina, Joachim, Catharine, Ortiz, Cecilia, Besse, Céline, Johansson, Charlotte, Zoia, Chiara Paola, Laske, Christoph, Anastasiou, Costas, Palacio, Dana Lis, Politis, Daniel G, Janowitz, Daniel, Craig, David, Mann, David M, Neary, David, Jürgen, Deckert, Daian, Delphine, Belezhanska, Diyana, Kohler, Eduardo, Castaño, Eduardo M, Koutsouraki, Effrosyni, Chipi, Elena, De Roeck, Ellen, Costantini, Emanuele, Vardy, Emma R L C, Piras, Fabrizio, Roveta, Fausto, Piras, Federica, Prestia, Federico Ariel, Assogna, Francesca, Salani, Francesca, Sala, Gessica, Lacidogna, Giordano, Novack, Gisela, Wilcock, Gordon, Thonberg, Håkan, Kölsch, Heike, Weber, Heike, Boecker, Henning, Etchepareborda, Ignacio, Piaceri, Irene, Tuomilehto, Jaakko, Lindström, Jaana, Laczo, Jan, Johnston, Janet, Deleuze, Jean-François, Harris, Jenny, Schott, Jonathan M, Priller, Josef, Bacha, Juan Ignacio, Snowden, Julie, Lisso, Julieta, Mihova, Kalina Yonkova, Traykov, Latchezar, Morelli, Laura, Brusco, Luis Ignacio, Rainer, Malik, Takalo, Mari, Bjerke, Maria, Del Zompo, Maria, Serpente, Maria, Sanchez Abalos, Mariana, Rios, Mario, Peltonen, Markku, Herrman, Martin J, Kohler, Matias, Rojo, Matias, Jones, Matthew, Orsini, Michela, Medel, Nancy, Olivar, Natividad, Fox, Nick C, Salvadori, Nicola, Hooper, Nigel M, Galeano, Pablo, Solis, Patricia, Bastiani, Patrizia, Passmore, Peter, Heun, Reinhard, Antikainen, Riitta, Olaso, Robert, Perneczky, Robert, Germani, Sandra, López-García, Sara, Love, Seth, Mehrabian, Shima, Bagnoli, Silvia, Kochen, Silvia, Andreoni, Simona, Teipel, Stefan, Todd, Stephen, Pickering-Brown, Stuart, Natunen, Teemu, Tegos, Thomas, Laatikainen, Tiina, Strandberg, Timo, Polvikoski, Tuomo M, Matoska, Vaclav, Ciullo, Valentina, Cores, Valeria, Solfrizzi, Vincenzo, Lisetti, Viviana, Sevillano, Zulma, Abdelnour, C., Aguilera, N., Alarcon, E., Alegret, M., Benaque, A., Boada, M., Buendia, M., Cañabate, P., Carracedo, A., Corbatón-Anchuelo, A., de Rojas, I., Diego, S., Espinosa, A., Gailhajenet, A., García-González, P., Gil, S., Guitart, M., González-Pérez, A., 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., 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., 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., Martín Montes, A., Martínez, B., Martínez, C., Martínez, V., Martínez-Lage Álvarez, P., Medina, M., Mendioroz Iriarte, M., Menéndez-González, 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., Sanchez Del Valle Díaz, R., Sánchez-Juan, P., Sastre, I., Vicente, M. P., Vigo-Ortega, R., Vivancos, L., Macleod, C., McCracken, C., Brayne, Carol, Bresner, Catherine, Grozeva, Detelina, Bellou, Eftychia, Sommerville, Ewen W, Matthews, F., Leonenko, Ganna, Menzies, Georgina, Windle, Gill, Harwood, Janet, Phillips, Judith, Bennett, K., Luckuck, Lauren, Clare, Linda, Woods, Robert, Saad, Salha, Burholt, Vanessa, Rongve, Arvid, Brussels Heritage Lab, Clinical sciences, Neuroprotection & Neuromodulation, and Neurology

Subjects
polygenic risk scores, Multidisciplinary, Common variants, Neuroscience(all), neurology, Medizin, General Physics and Astronomy, ddc:500, General Chemistry, Alzheimer's disease, General Biochemistry, Genetics and Molecular Biology, RISK STRATIFICATION
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. CA extern

Published
2023
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17. Human iPSC-Derived Hippocampal Spheroids: An Innovative Tool for Stratifying Alzheimer Disease Patient-Specific Cellular Phenotypes and Developing Therapies

Author

Pomeshchik, Yuriy, primary, Klementieva, Oxana, additional, Gil, Jeovanis, additional, Martinsson, Isak, additional, Hansen, Marita Grønning, additional, de Vries, Tessa, additional, Sancho-Balsells, Anna, additional, Russ, Kaspar, additional, Savchenko, Ekaterina, additional, Collin, Anna, additional, Vaz, Ana Rita, additional, Bagnoli, Silvia, additional, Nacmias, Benedetta, additional, Rampon, Claire, additional, Sorbi, Sandro, additional, Brites, Dora, additional, Marko-Varga, György, additional, Kokaia, Zaal, additional, Rezeli, Melinda, additional, Gouras, Gunnar K., additional, and Roybon, Laurent, additional

Published
2023
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18. Differences and Similarities in Empathy Deficit and Its Neural Basis between Logopenic and Amnesic Alzheimer’s Disease

Author

Giacomucci, Giulia, primary, Polito, Cristina, additional, Berti, Valentina, additional, Padiglioni, Sonia, additional, Galdo, Giulia, additional, Mazzeo, Salvatore, additional, Bergamin, Enrico, additional, Moschini, Valentina, additional, Morinelli, Carmen, additional, Nuti, Claudia, additional, De Cristofaro, Maria Teresa, additional, Ingannato, Assunta, additional, Bagnoli, Silvia, additional, Nacmias, Benedetta, additional, Sorbi, Sandro, additional, and Bessi, Valentina, additional

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2023
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19. Alzheimer’s Disease CSF Biomarker Profiles in Idiopathic Normal Pressure Hydrocephalus

Author

Mazzeo, Salvatore, primary, Emiliani, Filippo, additional, Bagnoli, Silvia, additional, Padiglioni, Sonia, additional, Del Re, Lorenzo Maria, additional, Giacomucci, Giulia, additional, Balestrini, Juri, additional, Ingannato, Assunta, additional, Moschini, Valentina, additional, Morinelli, Carmen, additional, Galdo, Giulia, additional, Polito, Cristina, additional, Ferrari, Camilla, additional, Pansini, Gastone, additional, Della Puppa, Alessandro, additional, Sorbi, Sandro, additional, Nacmias, Benedetta, additional, and Bessi, Valentina, additional

Published
2022
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20. Exploring Links Between Psychosis and Frontotemporal Dementia Using Multimodal Machine Learning: Dementia Praecox Revisited

Author

Koutsouleris, Nikolaos, Pantelis, Christos, Kambeitz, Joseph, Toivonen, Anna, Turtonen, Otto, Botterweck, Sonja, Kluthausen, Norman, Antoch, Gerald, Caspers, Julian, Wittsack, Hans-Jörg, Blasi, Giuseppe, Pergola, Giulio, Caforio, Grazia, Salokangas, Raimo K R, Fazio, Leonardo, Quarto, Tiziana, Gelao, Barbara, Romano, Raffaella, Andriola, Ileana, Falsetti, Andrea, Barone, Marina, Passiatore, Roberta, Sangiuliano, Marina, Surmann, Marian, Hietala, Jarmo, Bienek, Olga, Dannlowski, Udo, Solana, Ana Beatriz, Abraham, Manuela, Schirmer, Timo, Ferro, Adele, Re, Marta, Sberna, Maurizio, D'Agostino, Armando, Del Fabro, Lorenzo, Bertolino, Alessandro, Perna, Giampaolo, Nobile, Maria, Balestrieri, Matteo, Bonivento, Carolina, Cabras, Giuseppe, Fabbro, Franco, Delvecchio, Giuseppe, Maggioni, Eleonora, Squarcina, Letizia, Gritti, Davide, Brambilla, Paolo, Rossetti, Maria Gloria, Ferrari, Raffaele, Hernandez, Dena Michelle Godwin, Nalls, Michael, Rohrer, Jonathan, Ramasamy, Adaikalavan, Kwok, John, Dobson-Stone, Carol, Brooks, William, Schofield, Peter, Upthegrove, Rachel, Halliday, Glenda, Hodges, John, Piguet, Olivier, Bartley, Lauren, Thompson, Elizabeth, Hernández, Isabel, Ruiz, Agustín, Boada, Mercè, Borroni, Barbara, Padovani, Alessandro, Wood, Stephen J, Cruchaga, Carlos, Cairns, Nigel, Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Forloni, Gianluigi, Albani, Diego, Galimberti, Daniela, Fenoglio, Chiara, Serpente, Maria, Lencer, Rebekka, Scarpini, Elio, Clarimón, Jordi, Lleó, Alberto, Blesa, Rafael, Landqvist Waldö, Maria, Nilsson, Karin, Nilsson, Christer, Mackenzie, Ian R.A., Hsiung, Ging-Yuek, Mann, David, Borgwardt, Stefan, Grafman, Jordan, Morris, Christopher, Attems, Johannes, McKeith, Ian, Thomas, Alan, Pietrini, Pietro, Huey, Edward, Wassermann, Eric, Baborie, Atik, Jaros, Evelyn, Maj, Carlo, Tierney, Michael, Pastor, Pau, Razquin, Cristina, Ortega-Cubero, Sara, Alonso, Elena, Perneczky, Robert, Alexopoulos, Panagiotis, Kurz, Alexander, Rainero, Innocenzo, Rubino, Elisa, Velakoulis, Dennis, Nöthen, Markus M., Pinessi, Lorenzo, Rogaeva, Ekaterina, George-Hyslop, Peter, Rossi, Giacomina, Tagliavini, Fabrizio, Giaccone, Giorgio, Rowe, James, Schlachetzki, Johannes, Uphill, James, Collinge, John, Degenhardt, Franziska, Mead, Simon, Van Deerlin, Vivianna, Marschhauser, Anke, Regenbrecht, Frank, Thoene-Otto, Angelika, Gordulla, Jannis, Ballarini, Tommaso, Engel, Annerose, Pino, Daniele, Leuthold, Dominique, Polyakova, Maryna, Naumann, Heike, Grossman, Murray, Trojanowski, John Q, van der Zee, Julie, Van Broeckhofen, Christine, Cappa, Stefano F, Le Ber, Isabelle, Hannequin, Didier, Golfier, Véronique, Vercelletto, Martine, Mueller, Karsten, Brice, Alexis, Nacmias, Benedetta, Sorbi, Sandro, Bagnoli, Silvia, Piaceri, Irene, Nielsen, Jørgen E, Hjermind, Lena E, Riemenschneider, Matthias, Mayhaus, Manuel, Ibach, Bernd, Villringer, Arno, Gasparoni, Gilles, Pichler, Sabrina, Gu, Wei, Rossor, Martin N, Fox, Nick C, Warren, Jason D, Spillantini, Maria Grazia, Morris, Huw R, Rizzu, Patrizia, Heutink, Peter, Danek, Adrian, Snowden, Julie S, Rollinson, Sara, Richardson, Anna, Gerhard, Alexander, Bruni, Amalia C, Maletta, Raffaele, Frangipane, Francesca, Cupidi, Chiara, Bernardi, Livia, Anfossi, Maria, Fassbender, Klaus, Gallo, Maura, Conidi, Maria Elena, Smirne, Nicoletta, Rademakers, Rosa, Baker, Matt, Dickson, Dennis W, Graff-Radford, Neill R, Petersen, Ronald C, Knopman, David S, Josephs, Keith A, Fliessbach, Klaus, Boeve, Bradley F, Parisi, Joseph E, Seeley, William W, Miller, Bruce L, Karydas, Anna M, Rosen, Howard, van Swieten, John C, Dopper, Elise Gp, Seelaar, Harro, Pijnenburg, Yolande Al, Jahn, Holger, Scheltens, Philip, Logroscino, Giancarlo, Capozzo, Rosa, Novelli, Valeria, Puca, Annibale A, Franceschi, Massimo, Postiglione, Alfredo, Milan, Graziella, Sorrentino, Paolo, Kristiansen, Mark, Kornhuber, Johannes, Chiang, Huei-Hsin, Graff, Caroline, Pasquier, Florence, Rollin, Adeline, Deramecourt, Vincent, Lebouvier, Thibaud, Kapogiannis, Dimitrios, Ferrucci, Luigi, Pickering-Brown, Stuart, Singleton, Andrew B, McGuire, Philip, Landwehrmeyer, Bernhard, Hardy, John, Momeni, Parastoo, Barthel, Henryk, Elisa, Semler, Jolina, Lombardi, Christine, von Arnim, Felix, Oberahauser, Kai, Schumacher, Jan, Lehmbeck, Juan-Manuel, Maler, Anderl-Straub, Sarah, Tanja, Richter-Schmidinger, Anke, Hammer-Kaspereit, Timo, Oberstein, Felix, Müller-Sarnowski, Carola, Roßmeier, Albert, Ludolph, Jan, Kassubek, Anja, Schneider, Johannes, Levin, Prudlo, Johannes, Synofzik, Matthis, Wiltfang, Jens, Riedl, Lina, Diehl-Schmid, Janine, Otto, Markus, Meisenzahl, Eva, Falkai, Peter, Dwyer, Dominic B, Schroeter, Matthias L, Consortium, the PRONIA, Haas, Shalaila, Hasan, Alkomiet, Hoff, Claudius, Khanyaree, Ifrah, Melo, Aylin, Muckenhuber-Sternbauer, Susanna, Köhler, Yanis, Urquijo-Castro, Maria-Fernanda, Öztürk, Ömer, Penzel, Nora, Rangnick, Adrian, von Saldern, Sebastian, Spangemacher, Moritz, Tupac, Ana, Weiske, Johanna, Wosgien, Antonia, Krämer, Camilla, Blume, Karsten, Paul, Riya, Hedderich, Dennis, Julkowski, Dominika, Kaiser, Nathalie, Lichtenstein, Thorsten, Milz, Ruth, Nikolaides, Alexandra, Pilgram, Tanja, Seves, Mauro, Wassen, Martina, Andreou, Christina, Dong, Sen, Egloff, Laura, Harrisberger, Fabienne, Heitz, Ulrike, Lenz, Claudia, Leanza, Letizia, Mackintosh, Amatya, Smieskova, Renata, Studerus, Erich, Walter, Anna, Widmayer, Sonja, Popovic, David, Day, Chris, Lowri Griffiths, Sian, Iqbal, Mariam, Pelton, Mirabel, Mallikarjun, Pavan, Stainton, Alexandra, Lin, Ashleigh, Lalousis, Paris, Denissoff, Alexander, Ellilä, Anu, Oeztuerk, Oemer, From, Tiina, Heinimaa, Markus, Ilonen, Tuula, Jalo, Päivi, Laurikainen, Heikki, Luutonen, Antti, Mäkela, Akseli, Paju, Janina, Pesonen, Henri, Säilä, Reetta-Liina, International FTD-Genetics Consortium (IFGC), German Frontotemporal Lobar Degeneration (FTLD) Consortium, PRONIA Consortium, and International FTD-Genetics Consortium Consortium

Subjects
Adult, Male, Medizin, genetics [Alzheimer Disease], genetics [Psychotic Disorders], Neuropsychological Tests, diagnostic imaging [Frontotemporal Dementia], diagnostic imaging [Psychotic Disorders], Machine Learning, methods [Magnetic Resonance Imaging], Brain, Female, Humans, Magnetic Resonance Imaging, Alzheimer Disease, Frontotemporal Dementia, Psychotic Disorders, Schizophrenia, pathology [Brain], genetics [Schizophrenia], ddc:610, diagnostic imaging [Brain], genetics [Frontotemporal Dementia], Settore MED/25 - Psichiatria, Psychiatry and Mental health, diagnostic imaging [Schizophrenia], diagnostic imaging [Alzheimer Disease]
Abstract

Weitere Nicht-UDE Autoren sind nicht genannt. Importance: The behavioral and cognitive symptoms of severe psychotic disorders overlap with those seen in dementia. However, shared brain alterations remain disputed, and their relevance for patients in at-risk disease stages has not been explored so far. Objective: To use machine learning to compare the expression of structural magnetic resonance imaging (MRI) patterns of behavioral-variant frontotemporal dementia (bvFTD), Alzheimer disease (AD), and schizophrenia; estimate predictability in patients with bvFTD and schizophrenia based on sociodemographic, clinical, and biological data; and examine prognostic value, genetic underpinnings, and progression in patients with clinical high-risk (CHR) states for psychosis or recent-onset depression (ROD). Design, Setting, and Participants: This study included 1870 individuals from 5 cohorts, including (1) patients with bvFTD (n = 108), established AD (n = 44), mild cognitive impairment or early-stage AD (n = 96), schizophrenia (n = 157), or major depression (n = 102) to derive and compare diagnostic patterns and (2) patients with CHR (n = 160) or ROD (n = 161) to test patterns' prognostic relevance and progression. Healthy individuals (n = 1042) were used for age-related and cohort-related data calibration. Data were collected from January 1996 to July 2019 and analyzed between April 2020 and April 2022. Main Outcomes and Measures: Case assignments based on diagnostic patterns; sociodemographic, clinical, and biological data; 2-year functional outcomes and genetic separability of patients with CHR and ROD with high vs low pattern expression; and pattern progression from baseline to follow-up MRI scans in patients with nonrecovery vs preserved recovery. Results: Of 1870 included patients, 902 (48.2%) were female, and the mean (SD) age was 38.0 (19.3) years. The bvFTD pattern comprising prefrontal, insular, and limbic volume reductions was more expressed in patients with schizophrenia (65 of 157 [41.2%]) and major depression (22 of 102 [21.6%]) than the temporo-limbic AD patterns (28 of 157 [17.8%] and 3 of 102 [2.9%], respectively). bvFTD expression was predicted by high body mass index, psychomotor slowing, affective disinhibition, and paranoid ideation (R2= 0.11). The schizophrenia pattern was expressed in 92 of 108 patients (85.5%) with bvFTD and was linked to the C9orf72 variant, oligoclonal banding in the cerebrospinal fluid, cognitive impairment, and younger age (R2= 0.29). bvFTD and schizophrenia pattern expressions forecasted 2-year psychosocial impairments in patients with CHR and were predicted by polygenic risk scores for frontotemporal dementia, AD, and schizophrenia. Findings were not associated with AD or accelerated brain aging. Finally, 1-year bvFTD/schizophrenia pattern progression distinguished patients with nonrecovery from those with preserved recovery. Conclusions and Relevance: Neurobiological links may exist between bvFTD and psychosis focusing on prefrontal and salience system alterations. Further transdiagnostic investigations are needed to identify shared pathophysiological processes underlying the neuroanatomical interface between the 2 disease spectra.

Published
2022
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21. CAG Repeats Within the Non-pathological Range in the HTT Gene Influence Personality Traits in Patients With Subjective Cognitive Decline: A 13-Year Follow-Up Study

Author

Moschini, Valentina, primary, Mazzeo, Salvatore, additional, Bagnoli, Silvia, additional, Padiglioni, Sonia, additional, Emiliani, Filippo, additional, Giacomucci, Giulia, additional, Morinelli, Carmen, additional, Ingannato, Assunta, additional, Freni, Tommaso, additional, Belloni, Laura, additional, Ferrari, Camilla, additional, Sorbi, Sandro, additional, Nacmias, Benedetta, additional, and Bessi, Valentina, additional

Published
2022
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22. Clinical, Neurophysiological, and Genetic Predictors of Recovery in Patients With Severe Acquired Brain Injuries (PRABI): A Study Protocol for a Longitudinal Observational Study

Author

Hakiki, Bahia, primary, Donnini, Ida, additional, Romoli, Anna Maria, additional, Draghi, Francesca, additional, Maccanti, Daniela, additional, Grippo, Antonello, additional, Scarpino, Maenia, additional, Maiorelli, Antonio, additional, Sterpu, Raisa, additional, Atzori, Tiziana, additional, Mannini, Andrea, additional, Campagnini, Silvia, additional, Bagnoli, Silvia, additional, Ingannato, Assunta, additional, Nacmias, Benedetta, additional, De Bellis, Francesco, additional, Estraneo, Anna, additional, Carli, Valentina, additional, Pasqualone, Eugenia, additional, Comanducci, Angela, additional, Navarro, Jorghe, additional, Carrozza, Maria Chiara, additional, Macchi, Claudio, additional, and Cecchi, Francesca, additional

Published
2022
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23. Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia

Author

Swarup, Vivek, Hinz, Flora I., Rexach, Jessica E., Noguchi, Ken-ichi, Toyoshiba, Hiroyoshi, Oda, Akira, Hirai, Keisuke, Sarkar, Arjun, Seyfried, Nicholas T., Cheng, Chialin, Haggarty, Stephen J., Ferrari, Raffaele, Rohrer, Jonathan D., Ramasamy, Adaikalavan, Hardy, John, Hernandez, Dena G., Nalls, Michael A., Singleton, Andrew B., Kwok, John B. J., Dobson-Stone, Carol, Brooks, William S., Schofield, Peter R., Halliday, Glenda M., Hodges, John R., Piguet, Olivier, Bartley, Lauren, Thompson, Elizabeth, Haan, Eric, Hernández, Isabel, Ruiz, Agustín, Boada, Mercè, Borroni, Barbara, Padovani, Alessandro, Cairns, Nigel J., Cruchaga, Carlos, Binetti, Giuliano, Ghidoni, Roberta, Benussi, Luisa, Forloni, Gianluigi, Albani, Diego, Galimberti, Daniela, Fenoglio, Chiara, Serpente, Maria, Scarpini, Elio, Clarimón, Jordi, Lleó, Alberto, Blesa, Rafael, Waldö, Maria Landqvist, Nilsson, Karin, Nilsson, Christer, Mackenzie, Ian R. A., Hsiung, Ging-Yuek R., Mann, David M. A., Grafman, Jordan, Morris, Christopher M., Attems, Johannes, Griffiths, Timothy D., McKeith, Ian G., Thomas, Alan J., Jaros, Evelyn, Pietrini, Pietro, Huey, Edward D., Wassermann, Eric M., Tierney, Michael C., Baborie, Atik, Pastor, Pau, Ortega-Cubero, Sara, Razquin, Cristina, Alonso, Elena, Perneczky, Robert, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Kurz, Alexander, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Rogaeva, Ekaterina, George-Hyslop, Peter St., Rossi, Giacomina, Tagliavini, Fabrizio, Giaccone, Giorgio, Rowe, James B., Schlachetzki, Johannes C. M., Uphill, James, Collinge, John, Mead, Simon, Danek, Adrian, Van Deerlin, Vivianna M., Grossman, Murray, Trojanowski, John Q., Pickering-Brown, Stuart, Momeni, Parastoo, van der Zee, Julie, Cruts, Marc, Van Broeckhoven, Christine, Cappa, Stefano F., Leber, Isabelle, Brice, Alexis, Hannequin, Didier, Golfier, Véronique, Vercelletto, Martine, Nacmias, Benedetta, Sorbi, Sandro, Bagnoli, Silvia, Piaceri, Irene, Nielsen, Jørgen E., Hjermind, Lena E., Riemenschneider, Matthias, Mayhaus, Manuel, Gasparoni, Gilles, Pichler, Sabrina, Ibach, Bernd, Rossor, Martin N., Fox, Nick C., Warren, Jason D., Spillantini, Maria Grazia, Morris, Huw R., Rizzu, Patrizia, Heutink, Peter, Snowden, Julie S., Rollinson, Sara, Gerhard, Alexander, Richardson, Anna, Bruni, Amalia C., Maletta, Raffaele, Frangipane, Francesca, Cupidi, Chiara, Bernardi, Livia, Anfossi, Maria, Gallo, Maura, Conidi, Maria Elena, Smirne, Nicoletta, Rademakers, Rosa, Baker, Matt, Dickson, Dennis W., Graff-Radford, Neill R., Petersen, Ronald C., Knopman, David, Josephs, Keith A., Boeve, Bradley F., Parisi, Joseph E., Miller, Bruce L., Karydas, Anna M., Rosen, Howard, Seeley, William W., van Swieten, John C., Dopper, Elise G. P., Seelaar, Harro, Pijnenburg, Yolande A. L., Scheltens, Philip, Logroscino, Giancarlo, Capozzo, Rosa, Novelli, Valeria, Puca, Annibale A., Franceschi, Massimo, Postiglione, Alfredo, Milan, Graziella, Sorrentino, Paolo, Kristiansen, Mark, Chiang, Huei-Hsin, Graff, Caroline, Pasquier, Florence, Rollin, Adeline, Deramecourt, Vincent, Lebouvier, Thibaud, Ferrucci, Luigi, Kapogiannis, Dimitrios, Lah, James J., Levey, Allan I., Kondou, Shinichi, Geschwind, Daniel H., Int Frontotemporal Dementia Gen, Swarup, Vivek, Hinz, Flora I., Rexach, Jessica E., Noguchi, Ken-ichi, Toyoshiba, Hiroyoshi, Oda, Akira, Hirai, Keisuke, Sarkar, Arjun, Seyfried, Nicholas T., Cheng, Chialin, Haggarty, Stephen J., Ferrari, Raffaele, Rohrer, Jonathan D., Ramasamy, Adaikalavan, Hardy, John, Hernandez, Dena G., Nalls, Michael A., Singleton, Andrew B., Kwok, John B. J., Dobson-Stone, Carol, Brooks, William S., Schofield, Peter R., Halliday, Glenda M., Hodges, John R., Piguet, Olivier, Bartley, Lauren, Thompson, Elizabeth, Haan, Eric, Hernández, Isabel, Ruiz, Agustín, Boada, Mercè, Borroni, Barbara, Padovani, Alessandro, Cairns, Nigel J., Cruchaga, Carlo, Binetti, Giuliano, Ghidoni, Roberta, Benussi, Luisa, Forloni, Gianluigi, Albani, Diego, Galimberti, Daniela, Fenoglio, Chiara, Serpente, Maria, Scarpini, Elio, Clarimón, Jordi, Lleó, Alberto, Blesa, Rafael, Waldö, Maria Landqvist, Nilsson, Karin, Nilsson, Christer, Mackenzie, Ian R. A., Hsiung, Ging-Yuek R., Mann, David M. A., Grafman, Jordan, Morris, Christopher M., Attems, Johanne, Griffiths, Timothy D., Mckeith, Ian G., Thomas, Alan J., Jaros, Evelyn, Pietrini, Pietro, Huey, Edward D., Wassermann, Eric M., Tierney, Michael C., Baborie, Atik, Pastor, Pau, Ortega-Cubero, Sara, Razquin, Cristina, Alonso, Elena, Perneczky, Robert, Diehl-Schmid, Janine, Alexopoulos, Panagioti, Kurz, Alexander, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Rogaeva, Ekaterina, George-Hyslop, Peter St., Rossi, Giacomina, Tagliavini, Fabrizio, Giaccone, Giorgio, Rowe, James B., Schlachetzki, Johannes C. M., Uphill, Jame, Collinge, John, Mead, Simon, Danek, Adrian, Van Deerlin, Vivianna M., Grossman, Murray, Trojanowski, John Q., Pickering-Brown, Stuart, Momeni, Parastoo, van der Zee, Julie, Cruts, Marc, Van Broeckhoven, Christine, Cappa, Stefano F., Leber, Isabelle, Brice, Alexi, Hannequin, Didier, Golfier, Véronique, Vercelletto, Martine, Nacmias, Benedetta, Sorbi, Sandro, Bagnoli, Silvia, Piaceri, Irene, Nielsen, Jørgen E., Hjermind, Lena E., Riemenschneider, Matthia, Mayhaus, Manuel, Gasparoni, Gille, Pichler, Sabrina, Ibach, Bernd, Rossor, Martin N., Fox, Nick C., Warren, Jason D., Spillantini, Maria Grazia, Morris, Huw R., Rizzu, Patrizia, Heutink, Peter, Snowden, Julie S., Rollinson, Sara, Gerhard, Alexander, Richardson, Anna, Bruni, Amalia C., Maletta, Raffaele, Frangipane, Francesca, Cupidi, Chiara, Bernardi, Livia, Anfossi, Maria, Gallo, Maura, Conidi, Maria Elena, Smirne, Nicoletta, Rademakers, Rosa, Baker, Matt, Dickson, Dennis W., Graff-Radford, Neill R., Petersen, Ronald C., Knopman, David, Josephs, Keith A., Boeve, Bradley F., Parisi, Joseph E., Miller, Bruce L., Karydas, Anna M., Rosen, Howard, Seeley, William W., van Swieten, John C., Dopper, Elise G. P., Seelaar, Harro, Pijnenburg, Yolande A. L., Scheltens, Philip, Logroscino, Giancarlo, Capozzo, Rosa, Novelli, Valeria, Puca, Annibale A., Franceschi, Massimo, Postiglione, Alfredo, Milan, Graziella, Sorrentino, Paolo, Kristiansen, Mark, Chiang, Huei-Hsin, Graff, Caroline, Pasquier, Florence, Rollin, Adeline, Deramecourt, Vincent, Lebouvier, Thibaud, Ferrucci, Luigi, Kapogiannis, Dimitrio, Lah, James J., Levey, Allan I., Kondou, Shinichi, and Geschwind, Daniel H.

Subjects
Proteomics, Genetics and Molecular Biology (all), 0301 basic medicine, Messenger, Gene regulatory network, Inbred C57BL, Biochemistry, Transgenic, Mice, 0302 clinical medicine, Gene Regulatory Networks, Regulation of gene expression, Cell Death, Drug discovery, Neurodegeneration, Neurodegenerative Diseases, General Medicine, Chemistry, Frontotemporal Dementia, 030220 oncology & carcinogenesis, Frontotemporal dementia, Evolution, Systems biology, Genetic Vectors, Animals, Dementia, Disease Models, Animal, Gene Expression Regulation, Genetic Predisposition to Disease, Humans, Mice, Inbred C57BL, Mice, Transgenic, MicroRNAs, RNA, Messenger, Reproducibility of Results, Transcriptome, tau Proteins, Evolution, Molecular, Computational biology, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, microRNA, medicine, Biochemistry, Genetics and Molecular Biology (all), Animal, Molecular, medicine.disease, 030104 developmental biology, Disease Models, RNA, Human medicine
Abstract

Identifying the mechanisms through which genetic risk causes dementia is an imperative for new therapeutic development. Here, we apply a multistage, systems biology approach to elucidate the disease mechanisms in frontotemporal dementia. We identify two gene coexpression modules that are preserved in mice harboring mutations in MAPT, GRN and other dementia mutations on diverse genetic backgrounds. We bridge the species divide via integration with proteomic and transcriptomic data from the human brain to identify evolutionarily conserved, disease-relevant networks. We find that overexpression of miR-203, a hub of a putative regulatory microRNA (miRNA) module, recapitulates mRNA coexpression patterns associated with disease state and induces neuronal cell death, establishing this miRNA as a regulator of neurodegeneration. Using a database of drug-mediated gene expression changes, we identify small molecules that can normalize the disease-associated modules and validate this experimentally. Our results highlight the utility of an integrative, cross-species network approach to drug discovery.

Published
2018
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24. Human iPSC-derived hippocampal spheroids: An innovative tool for stratifying Alzheimer disease patient-specific cellular phenotypes and developing therapies

Author

Pomeshchik, Yuriy, primary, Klementieva, Oxana, additional, Gil, Jeovanis, additional, Martinsson, Isak, additional, Hansen, Marita Grønning, additional, de Vries, Tessa, additional, Sancho-Balsells, Anna, additional, Russ, Kaspar, additional, Savchenko, Ekaterina, additional, Collin, Anna, additional, Vaz, Ana Rita, additional, Bagnoli, Silvia, additional, Nacmias, Benedetta, additional, Rampon, Claire, additional, Sorbi, Sandro, additional, Brites, Dora, additional, Marko-Varga, György, additional, Kokaia, Zaal, additional, Rezeli, Melinda, additional, Gouras, Gunnar K., additional, and Roybon, Laurent, additional

Published
2021
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26. Gene Expression Imputation Across Multiple Tissue Types Provides Insight Into the Genetic Architecture of Frontotemporal Dementia and Its Clinical Subtypes

Author

Reus, Lianne M., Pasaniuc, Bogdan, Posthuma, Danielle, Boltz, Toni, Ferrari, Raffaele, Hernandez, Dena G., Nalls, Michael A., Rohrer, Jonathan D., Ramasamy, Adaikalavan, Kwok, John B.J., Dobson-Stone, Carol, Brooks, William S., Schofield, Peter R., Halliday, Glenda M., Hodges, John R., Piguet, Olivier, Bartley, Lauren, Thompson, Elizabeth, Hernández, Isabel, Ruiz, Agustín, Boada, Mercè, Borroni, Barbara, Padovani, Alessandro, Cruchaga, Carlos, Cairns, Nigel J., Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Forloni, Gianluigi, Galimberti, Daniela, Fenoglio, Chiara, Serpente, Maria, Scarpini, Elio, Clarimón, Jordi, Lleó, Alberto, Blesa, Rafael, Waldö, Maria Landqvist, Nilsson, Karin, Nilsson, Christer, Mackenzie, Ian R.A., Hsiung, Ging Yuek R., Mann, David M.A., Grafman, Jordan, Morris, Christopher M., Attems, Johannes, Griffiths, Timothy D., McKeith, Ian G., Thomas, Alan J., Pietrini, Pietro, Huey, Edward D., Wassermann, Eric M., Baborie, Atik, Jaros, Evelyn, Tierney, Michael C., Pastor, Pau, Razquin, Cristina, Ortega-Cubero, Sara, Alonso, Elena, Perneczky, Robert, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Kurz, Alexander, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Rogaeva, Ekaterina, St. George-Hyslop, Peter, Rossi, Giacomina, Tagliavini, Fabrizio, Giaccone, Giorgio, Rowe, James B., Schlachetzki, Johannes C.M., Uphill, James, Collinge, John, Mead, Simon, Danek, Adrian, Van Deerlin, Vivianna M., Grossman, Murray, Trojanowski, John Q., van der Zee, Julie, Van Broeckhoven, Christine, Cappa, Stefano F., Le Ber, Isabelle, Hannequin, Didier, Golfier, Véronique, Vercelletto, Martine, Brice, Alexis, Nacmias, Benedetta, Sorbi, Sandro, Bagnoli, Silvia, Piaceri, Irene, Nielsen, Jørgen E., Hjermind, Lena E., Riemenschneider, Matthias, Mayhaus, Manuel, Ibach, Bernd, Gasparoni, Gilles, Pichler, Sabrina, Gu, Wei, Rossor, Martin N., Fox, Nick C., Warren, Jason D., Spillantini, Maria Grazia, Morris, Huw R., Rizzu, Patrizia, Heutink, Peter, Snowden, Julie S., Rollinson, Sara, Richardson, Anna, Gerhard, Alexander, Bruni, Amalia C., Maletta, Raffaele, Frangipane, Francesca, Cupidi, Chiara, Bernardi, Livia, Anfossi, Maria, Gallo, Maura, Conidi, Maria Elena, Smirne, Nicoletta, Rademakers, Rosa, Baker, Matt, Dickson, Dennis W., Graff-Radford, Neill R., Petersen, Ronald C., Knopman, David, Josephs, Keith A., Boeve, Bradley F., Parisi, Joseph E., Seeley, William W., Miller, Bruce L., Karydas, Anna M., Rosen, Howard, van Swieten, John C., Dopper, Elise G.P., Seelaar, Harro, Pijnenburg, Yolande A.L., Scheltens, Philip, Logroscino, Giancarlo, Capozzo, Rosa, Novelli, Valeria, Puca, Annibale A., Franceschi, Massimo, Postiglione, Alfredo, Milan, Graziella, Sorrentino, Paolo, Kristiansen, Mark, Chiang, Huei Hsin, Graff, Caroline, Pasquier, Florence, Rollin, Adeline, Deramecourt, Vincent, Lebert, Florence, Kapogiannis, Dimitrios, Ferrucci, Luigi, Pickering-Brown, Stuart, Singleton, Andrew B., Hardy, John, Momeni, Parastoo, Ophoff, Roel A., Reus, Lianne M., Pasaniuc, Bogdan, Posthuma, Danielle, Boltz, Toni, Ferrari, Raffaele, Hernandez, Dena G., Nalls, Michael A., Rohrer, Jonathan D., Ramasamy, Adaikalavan, Kwok, John B.J., Dobson-Stone, Carol, Brooks, William S., Schofield, Peter R., Halliday, Glenda M., Hodges, John R., Piguet, Olivier, Bartley, Lauren, Thompson, Elizabeth, Hernández, Isabel, Ruiz, Agustín, Boada, Mercè, Borroni, Barbara, Padovani, Alessandro, Cruchaga, Carlos, Cairns, Nigel J., Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Forloni, Gianluigi, Galimberti, Daniela, Fenoglio, Chiara, Serpente, Maria, Scarpini, Elio, Clarimón, Jordi, Lleó, Alberto, Blesa, Rafael, Waldö, Maria Landqvist, Nilsson, Karin, Nilsson, Christer, Mackenzie, Ian R.A., Hsiung, Ging Yuek R., Mann, David M.A., Grafman, Jordan, Morris, Christopher M., Attems, Johannes, Griffiths, Timothy D., McKeith, Ian G., Thomas, Alan J., Pietrini, Pietro, Huey, Edward D., Wassermann, Eric M., Baborie, Atik, Jaros, Evelyn, Tierney, Michael C., Pastor, Pau, Razquin, Cristina, Ortega-Cubero, Sara, Alonso, Elena, Perneczky, Robert, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Kurz, Alexander, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Rogaeva, Ekaterina, St. George-Hyslop, Peter, Rossi, Giacomina, Tagliavini, Fabrizio, Giaccone, Giorgio, Rowe, James B., Schlachetzki, Johannes C.M., Uphill, James, Collinge, John, Mead, Simon, Danek, Adrian, Van Deerlin, Vivianna M., Grossman, Murray, Trojanowski, John Q., van der Zee, Julie, Van Broeckhoven, Christine, Cappa, Stefano F., Le Ber, Isabelle, Hannequin, Didier, Golfier, Véronique, Vercelletto, Martine, Brice, Alexis, Nacmias, Benedetta, Sorbi, Sandro, Bagnoli, Silvia, Piaceri, Irene, Nielsen, Jørgen E., Hjermind, Lena E., Riemenschneider, Matthias, Mayhaus, Manuel, Ibach, Bernd, Gasparoni, Gilles, Pichler, Sabrina, Gu, Wei, Rossor, Martin N., Fox, Nick C., Warren, Jason D., Spillantini, Maria Grazia, Morris, Huw R., Rizzu, Patrizia, Heutink, Peter, Snowden, Julie S., Rollinson, Sara, Richardson, Anna, Gerhard, Alexander, Bruni, Amalia C., Maletta, Raffaele, Frangipane, Francesca, Cupidi, Chiara, Bernardi, Livia, Anfossi, Maria, Gallo, Maura, Conidi, Maria Elena, Smirne, Nicoletta, Rademakers, Rosa, Baker, Matt, Dickson, Dennis W., Graff-Radford, Neill R., Petersen, Ronald C., Knopman, David, Josephs, Keith A., Boeve, Bradley F., Parisi, Joseph E., Seeley, William W., Miller, Bruce L., Karydas, Anna M., Rosen, Howard, van Swieten, John C., Dopper, Elise G.P., Seelaar, Harro, Pijnenburg, Yolande A.L., Scheltens, Philip, Logroscino, Giancarlo, Capozzo, Rosa, Novelli, Valeria, Puca, Annibale A., Franceschi, Massimo, Postiglione, Alfredo, Milan, Graziella, Sorrentino, Paolo, Kristiansen, Mark, Chiang, Huei Hsin, Graff, Caroline, Pasquier, Florence, Rollin, Adeline, Deramecourt, Vincent, Lebert, Florence, Kapogiannis, Dimitrios, Ferrucci, Luigi, Pickering-Brown, Stuart, Singleton, Andrew B., Hardy, John, Momeni, Parastoo, and Ophoff, Roel A.

Abstract

Background: The etiology of frontotemporal dementia (FTD) is poorly understood. To identify genes with predicted expression levels associated with FTD, we integrated summary statistics with external reference gene expression data using a transcriptome-wide association study approach. Methods: FUSION software was used to leverage FTD summary statistics (all FTD: n = 2154 cases, n = 4308 controls; behavioral variant FTD: n = 1337 cases, n = 2754 controls; semantic dementia: n = 308 cases, n = 616 controls; progressive nonfluent aphasia: n = 269 cases, n = 538 controls; FTD with motor neuron disease: n = 200 cases, n = 400 controls) from the International FTD-Genomics Consortium with 53 expression quantitative loci tissue type panels (n = 12,205; 5 consortia). Significance was assessed using a 5% false discovery rate threshold. Results: We identified 73 significant gene–tissue associations for FTD, representing 44 unique genes in 34 tissue types. Most significant findings were derived from dorsolateral prefrontal cortex splicing data (n = 19 genes, 26%). The 17q21.31 inversion locus contained 23 significant associations, representing 6 unique genes. Other top hits included SEC22B (a gene involved in vesicle trafficking), TRGV5, and ZNF302. A single gene finding (RAB38) was observed for behavioral variant FTD. For other clinical subtypes, no significant associations were observed. Conclusions: We identified novel candidate genes (e.g., SEC22B) and previously reported risk regions (e.g., 17q21.31) for FTD. Most significant associations were observed in dorsolateral prefrontal cortex splicing data despite the modest sample size of this reference panel. This suggests that our findings are specific to FTD and are likely to be biologically relevant highlights of genes at different FTD risk loci that are contributing to the disease pathology.

Published
2021

29. The Effect of CAG Repeats within the Non-Pathological Range in the HTT Gene on Cognitive Functions in Patients with Subjective Cognitive Decline and Mild Cognitive Impairment

Author

Bessi, Valentina, primary, Mazzeo, Salvatore, additional, Bagnoli, Silvia, additional, Giacomucci, Giulia, additional, Ingannato, Assunta, additional, Ferrari, Camilla, additional, Padiglioni, Sonia, additional, Franchi, Virginia, additional, Sorbi, Sandro, additional, and Nacmias, Benedetta, additional

Published
2021
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30. Dual Effect of PER2 C111G Polymorphism on Cognitive Functions across Progression from Subjective Cognitive Decline to Mild Cognitive Impairment

Author

Mazzeo, Salvatore, primary, Bessi, Valentina, additional, Bagnoli, Silvia, additional, Giacomucci, Giulia, additional, Balestrini, Juri, additional, Padiglioni, Sonia, additional, Tomaiuolo, Giulia, additional, Ingannato, Assunta, additional, Ferrari, Camilla, additional, Bracco, Laura, additional, Sorbi, Sandro, additional, and Nacmias, Benedetta, additional

Published
2021
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31. Predictors of Function, Activity, and Participation of Stroke Patients Undergoing Intensive Rehabilitation: A Multicenter Prospective Observational Study Protocol

Author

Hakiki, Bahia, primary, Paperini, Anita, additional, Castagnoli, Chiara, additional, Hochleitner, Ines, additional, Verdesca, Sonia, additional, Grippo, Antonello, additional, Scarpino, Maenia, additional, Maiorelli, Antonio, additional, Mosca, Irene Eleonora, additional, Gemignani, Paola, additional, Borsotti, Marco, additional, Gabrielli, Maria Assunta, additional, Salvadori, Emilia, additional, Poggesi, Anna, additional, Lucidi, Giulia, additional, Falsini, Catiuscia, additional, Gentilini, Monica, additional, Martini, Monica, additional, Luisi, Maria Luisa Eliana, additional, Biffi, Barbara, additional, Mainardi, Paolo, additional, Barretta, Teresa, additional, Pancani, Silvia, additional, Mannini, Andrea, additional, Campagnini, Silvia, additional, Bagnoli, Silvia, additional, Ingannato, Assunta, additional, Nacmias, Benedetta, additional, Macchi, Claudio, additional, Carrozza, Maria Chiara, additional, and Cecchi, Francesca, additional

Published
2021
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33. The Brain-Derived Neurotrophic Factor Val66Met Polymorphism Can Protect Against Cognitive Impairment in Multiple Sclerosis

Author

Portaccio, Emilio, primary, Bellinvia, Angelo, additional, Prestipino, Elio, additional, Nacmias, Benedetta, additional, Bagnoli, Silvia, additional, Razzolini, Lorenzo, additional, Pastò, Luisa, additional, Niccolai, Claudia, additional, Goretti, Benedetta, additional, Fonderico, Mattia, additional, Zimatore, Giovanni Bosco, additional, Losignore, Nunzia Alessandra, additional, Sorbi, Sandro, additional, and Amato, Maria Pia, additional

Published
2021
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34. Matching Clinical Diagnosis and Amyloid Biomarkers in Alzheimer’s Disease and Frontotemporal Dementia

Author

Giacomucci, Giulia, primary, Mazzeo, Salvatore, additional, Bagnoli, Silvia, additional, Casini, Matteo, additional, Padiglioni, Sonia, additional, Polito, Cristina, additional, Berti, Valentina, additional, Balestrini, Juri, additional, Ferrari, Camilla, additional, Lombardi, Gemma, additional, Ingannato, Assunta, additional, Sorbi, Sandro, additional, Nacmias, Benedetta, additional, and Bessi, Valentina, additional

Published
2021
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35. Influence of ApoE Genotype and Clock T3111C Interaction with Cardiovascular Risk Factors on the Progression to Alzheimer’s Disease in Subjective Cognitive Decline and Mild Cognitive Impairment Patients

Author

Bessi, Valentina, primary, Balestrini, Juri, additional, Bagnoli, Silvia, additional, Mazzeo, Salvatore, additional, Giacomucci, Giulia, additional, Padiglioni, Sonia, additional, Piaceri, Irene, additional, Carraro, Marco, additional, Ferrari, Camilla, additional, Bracco, Laura, additional, Sorbi, Sandro, additional, and Nacmias, Benedetta, additional

Published
2020
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36. Alzheimer's Disease Progression : Factors Influencing Cognitive Decline

Author

Ferrari, Camilla, Lombardi, Gemma, Polito, Cristina, Lucidi, Giulia, Bagnoli, Silvia, Piaceri, Irene, Nacmias, Benedetta, Berti, Valentina, Rizzuto, Debora, Fratiglioni, Laura, Sorbi, Sandro, Ferrari, Camilla, Lombardi, Gemma, Polito, Cristina, Lucidi, Giulia, Bagnoli, Silvia, Piaceri, Irene, Nacmias, Benedetta, Berti, Valentina, Rizzuto, Debora, Fratiglioni, Laura, and Sorbi, Sandro

Abstract

Background: Alzheimer's disease (AD) patients present high variability in the rate of cognitive decline. Despite the wide knowledge on factors influencing dementia risk, little is known on what accounts for AD progression. Previous studies on this topic have mainly analyzed each factor separately without taking into account the interaction between genetic and non-genetic factors. Objective: The aim of the present study is to evaluate the role of demographic, clinical, therapeutic, and genetic factors and their interaction on cognitive decline among newly diagnosed AD patients. Methods: We retrospectively selected 160 AD patients diagnosed at the Neurology Unit of Careggi University Hospital of Florence. We evaluated the occurrence of rapid cognitive changes defined as the worsening of more than four points at the Mini-Mental State Examination after 2-year follow up period. Results: Among the 160 AD patients, 50% presented rapid disease progression. Extrapyramidal signs at disease onset were predictors of worse outcome (OR 2.2), especially among Apolipoprotein E (APOE) epsilon 4 allele carriers, while the presence of family history for dementia decreased the risk of rapid progression by about 50%. Higher educated epsilon 4-carriers showed a slower AD progression. We identified the chronic use of aspirin as potential secondary preventative strategy for the non epsilon 4-carriers. Conclusion: At dementia onset, some clinical and demographic data can be predictors of future progression. The outcomes of the present study support the already hypothesized interaction between genetic and non-genetic factors during disease course and suggest genetic-based approaches.

Published
2018
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37. No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients.

Author

UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, Baradaran-Heravi, Yalda, Dillen, Lubina, Nguyen, Hung Phuoc, Van Mossevelde, Sara, Baets, Jonathan, De Jonghe, Peter, Engelborghs, Sebastiaan, De Deyn, Peter P, Vandenbulcke, Mathieu, Vandenberghe, Rik, Van Damme, Philip, Cras, Patrick, Salmon, Eric, Synofzik, Matthis, Heutink, Peter, Wilke, Carlo, Simon-Sanchez, Javier, Rojas-Garcia, Ricard, Turon-Sans, Janina, Lleó, Alberto, Illán-Gala, Ignacio, Clarimón, Jordi, Borroni, Barbara, Padovani, Alessandro, Pastor, Pau, Diez-Fairen, Monica, Aguilar, Miquel, Gelpi, Ellen, Sanchez-Valle, Raquel, Borrego-Ecija, Sergi, Matej, Radoslav, Parobkova, Eva, Nacmias, Benedetta, Sorbi, Sandro, Bagnoli, Silvia, de Mendonça, Alexandre, Ferreira, Catarina, Fraidakis, Matthew J, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Almeida, Maria Rosário, Santana, Isabel, Van Broeckhoven, Christine, van der Zee, Julie, BELNEU Consortium, EU EOD Consortium, Ivanoiu, Adrian, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, Baradaran-Heravi, Yalda, Dillen, Lubina, Nguyen, Hung Phuoc, Van Mossevelde, Sara, Baets, Jonathan, De Jonghe, Peter, Engelborghs, Sebastiaan, De Deyn, Peter P, Vandenbulcke, Mathieu, Vandenberghe, Rik, Van Damme, Philip, Cras, Patrick, Salmon, Eric, Synofzik, Matthis, Heutink, Peter, Wilke, Carlo, Simon-Sanchez, Javier, Rojas-Garcia, Ricard, Turon-Sans, Janina, Lleó, Alberto, Illán-Gala, Ignacio, Clarimón, Jordi, Borroni, Barbara, Padovani, Alessandro, Pastor, Pau, Diez-Fairen, Monica, Aguilar, Miquel, Gelpi, Ellen, Sanchez-Valle, Raquel, Borrego-Ecija, Sergi, Matej, Radoslav, Parobkova, Eva, Nacmias, Benedetta, Sorbi, Sandro, Bagnoli, Silvia, de Mendonça, Alexandre, Ferreira, Catarina, Fraidakis, Matthew J, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Almeida, Maria Rosário, Santana, Isabel, Van Broeckhoven, Christine, van der Zee, Julie, BELNEU Consortium, EU EOD Consortium, and Ivanoiu, Adrian

Abstract

We evaluated the genetic contribution of the T cell-restricted intracellular antigen-1 gene (TIA1) in a European cohort of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) patients. Exonic resequencing of TIA1 in 1120 patients (693 FTD, 341 ALS, 86 FTD-ALS) and 1039 controls identified in total 5 rare heterozygous missense variants, affecting the TIA1 low-complexity domain (LCD). Only 1 missense variant, p.Met290Thr, identified in a familial FTD patient with disease onset at 64 years, was absent from controls yet received a combined annotation-dependent depletion score of 11.42. By contrast, 3 of the 4 variants also detected in unaffected controls, p.Val294Glu, p.Gln318Arg, and p.Ala381Thr, had combined annotation-dependent depletion scores greater than 20. Our findings in a large European patient-control series indicate that variants in TIA1 are not a common cause of ALS and FTD. The observation of recurring TIA1 missense variants in unaffected individuals lead us to conclude that the exact genetic contribution of TIA1 to ALS and FTD pathogenesis remains to be further elucidated.

Published
2018

38. Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations:a genome-wide association study

Author

Pottier, Cyril, Zhou, Xiaolai, Perkerson, Ralph B, Baker, Matt, Jenkins, Gregory D, Serie, Daniel J, Ghidoni, Roberta, Benussi, Luisa, Binetti, Giuliano, López De Munain, Adolfo, Zulaica, Miren, Moreno, Fermin, Le Ber, Isabelle, Pasquier, Florence, Hannequin, Didier, Sánchez-Valle, Raquel, Antonell, Anna, Lladó, Albert, Parsons, Tammee M, Finch, Nicole A, Finger, Elizabeth C, Lippa, Carol F, Huey, Edward D, Neumann, Manuela, Heutink, Peter, Synofzik, Matthis, Wilke, Carlo, Rissman, Robert A, Slawek, Jaroslaw, Sitek, Emilia, Johannsen, Peter, Nielsen, Jørgen E, Ren, Yingxue, Van Blitterswijk, Marka, Dejesus-Hernandez, Mariely, Christopher, Elizabeth, Murray, Melissa E, Bieniek, Kevin F, Evers, Bret M, Ferrari, Camilla, Rollinson, Sara, Richardson, Anna, Scarpini, Elio, Fumagalli, Giorgio G, Padovani, Alessandro, Hardy, John, Momeni, Parastoo, Ferrari, Raffaele, Frangipane, Francesca, Maletta, Raffaele, Anfossi, Maria, Gallo, Maura, Petrucelli, Leonard, Suh, Eunran, Lopez, Oscar L, Wong, Tsz H, Van Rooij, Jeroen G J, Seelaar, Harro, Mead, Simon, Caselli, Richard J, Reiman, Eric M, Noel Sabbagh, Marwan, Kjolby, Mads, Nykjaer, Anders, Karydas, Anna M, Boxer, Adam L, Grinberg, Lea T, Grafman, Jordan, Spina, Salvatore, Oblak, Adrian, Mesulam, M-Marsel, Weintraub, Sandra, Geula, Changiz, Hodges, John R, Piguet, Olivier, Brooks, William S, Irwin, David J, Trojanowski, John Q, Lee, Edward B, Josephs, Keith A, Parisi, Joseph E, Ertekin-Taner, Nilüfer, Knopman, David S, Nacmias, Benedetta, Piaceri, Irene, Bagnoli, Silvia, Sorbi, Sandro, Gearing, Marla, Glass, Jonathan, Beach, Thomas G, Black, Sandra E, Masellis, Mario, Rogaeva, Ekaterina, Vonsattel, Jean-paul, Honig, Lawrence S, Kofler, Julia, Bruni, Amalia C, Snowden, Julie, Mann, David, Pickering-Brown, Stuart, Diehl-Schmid, Janine, Winkelmann, Juliane, Galimberti, Daniela, Graff, Caroline, Öijerstedt, Linn, Troakes, Claire, Al-Sarraj, Safa, Cruchaga, Carlos, Cairns, Nigel J, Rohrer, Jonathan D, Halliday, Glenda M, Kwok, John B, Van Swieten, John C, White, Charles L, Ghetti, Bernardino, Murell, Jill R, Mackenzie, Ian R A, Hsiung, Ging-Yuek R, Borroni, Barbara, Rossi, Giacomina, Tagliavini, Fabrizio, Wszolek, Zbigniew K, Petersen, Ronald C, Bigio, Eileen H, Grossman, Murray, Van Deerlin, Vivianna M, Seeley, William W, Miller, Bruce L, Graff-Radford, Neill R, Boeve, Bradley F, Dickson, Dennis W, Biernacka, Joanna M, Rademakers, Rosa, Pottier, Cyril, Zhou, Xiaolai, Perkerson, Ralph B, Baker, Matt, Jenkins, Gregory D, Serie, Daniel J, Ghidoni, Roberta, Benussi, Luisa, Binetti, Giuliano, López De Munain, Adolfo, Zulaica, Miren, Moreno, Fermin, Le Ber, Isabelle, Pasquier, Florence, Hannequin, Didier, Sánchez-Valle, Raquel, Antonell, Anna, Lladó, Albert, Parsons, Tammee M, Finch, Nicole A, Finger, Elizabeth C, Lippa, Carol F, Huey, Edward D, Neumann, Manuela, Heutink, Peter, Synofzik, Matthis, Wilke, Carlo, Rissman, Robert A, Slawek, Jaroslaw, Sitek, Emilia, Johannsen, Peter, Nielsen, Jørgen E, Ren, Yingxue, Van Blitterswijk, Marka, Dejesus-Hernandez, Mariely, Christopher, Elizabeth, Murray, Melissa E, Bieniek, Kevin F, Evers, Bret M, Ferrari, Camilla, Rollinson, Sara, Richardson, Anna, Scarpini, Elio, Fumagalli, Giorgio G, Padovani, Alessandro, Hardy, John, Momeni, Parastoo, Ferrari, Raffaele, Frangipane, Francesca, Maletta, Raffaele, Anfossi, Maria, Gallo, Maura, Petrucelli, Leonard, Suh, Eunran, Lopez, Oscar L, Wong, Tsz H, Van Rooij, Jeroen G J, Seelaar, Harro, Mead, Simon, Caselli, Richard J, Reiman, Eric M, Noel Sabbagh, Marwan, Kjolby, Mads, Nykjaer, Anders, Karydas, Anna M, Boxer, Adam L, Grinberg, Lea T, Grafman, Jordan, Spina, Salvatore, Oblak, Adrian, Mesulam, M-Marsel, Weintraub, Sandra, Geula, Changiz, Hodges, John R, Piguet, Olivier, Brooks, William S, Irwin, David J, Trojanowski, John Q, Lee, Edward B, Josephs, Keith A, Parisi, Joseph E, Ertekin-Taner, Nilüfer, Knopman, David S, Nacmias, Benedetta, Piaceri, Irene, Bagnoli, Silvia, Sorbi, Sandro, Gearing, Marla, Glass, Jonathan, Beach, Thomas G, Black, Sandra E, Masellis, Mario, Rogaeva, Ekaterina, Vonsattel, Jean-paul, Honig, Lawrence S, Kofler, Julia, Bruni, Amalia C, Snowden, Julie, Mann, David, Pickering-Brown, Stuart, Diehl-Schmid, Janine, Winkelmann, Juliane, Galimberti, Daniela, Graff, Caroline, Öijerstedt, Linn, Troakes, Claire, Al-Sarraj, Safa, Cruchaga, Carlos, Cairns, Nigel J, Rohrer, Jonathan D, Halliday, Glenda M, Kwok, John B, Van Swieten, John C, White, Charles L, Ghetti, Bernardino, Murell, Jill R, Mackenzie, Ian R A, Hsiung, Ging-Yuek R, Borroni, Barbara, Rossi, Giacomina, Tagliavini, Fabrizio, Wszolek, Zbigniew K, Petersen, Ronald C, Bigio, Eileen H, Grossman, Murray, Van Deerlin, Vivianna M, Seeley, William W, Miller, Bruce L, Graff-Radford, Neill R, Boeve, Bradley F, Dickson, Dennis W, Biernacka, Joanna M, and Rademakers, Rosa

Published
2018

39. Low Florbetapir PET Uptake and Normal Aβ1-42 Cerebrospinal Fluid in an APP Ala713Thr Mutation Carrier

Author

Lombardi, Gemma, Berti, Valentina, Tedde, Andrea, Bagnoli, Silvia, Piaceri, Irene, Polito, Cristina, Lucidi, Giulia, Ferrari, Camilla, Ginestroni, Andrea, Moretti, Marco, Pupi, Alberto, Nacmias, Benedetta, and Sorbi, Sandro

Subjects
mental disorders, APP Ala713Thr, familial Alzheimer's disease, florbetapir PET, frontotemporal dementia, Clinical Psychology, Geriatrics and Gerontology, Psychiatry and Mental Health
Published
2017

40. Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer’s disease

Author

de Roeck, Arne, van Den Bossche, Tobi, van der Zee, Julie, Verheijen, Jan, de Coster, Wouter, van Dongen, Jasper, Dillen, Lubina, Baradaran Heravi, Yalda, Heeman, Bavo, Sanchez Valle, Raquel, Lladó, Albert, Nacmias, Benedetta, Sorbi, Sandro, Gelpi, Ellen, Grau Rivera, Oriol, Gómez Tortosa, Estrella, Pastor, Pau, Ortega Cubero, Sara, Pastor, Maria A., Graff, Caroline, Thonberg, Håkan, Benussi, Luisa, Ghidoni, Roberta, Binetti, Giuliano, de Mendonça, Alexandre, Martins, Madalena, Borroni, Barbara, Padovani, Alessandro, Almeida, Maria Rosário, Santana, Isabel, Diehl Schmid, Janine, Alexopoulos, Panagiotis, Clarimon, Jordi, Lleó, Alberto, Fortea, Juan, Tsolaki, Magda, Koutroumani, Maria, Matěj, Radoslav, Rohan, Zdenek, de Deyn, Peter, Engelborghs, Sebastiaan, Cras, Patrick, van Broeckhoven, Christine, Sleegers, Kristel, Bessi, Valentina, Bagnoli, Silvia, Do Couto, Frederico Simões, Verdelho, Ana, Fratiglioni, Laura, Razquin, Cristina, Lorenzo, Elena, Iglesias, Elena, Seijo Martínez, Manuel, Rene, Ramon, Gascon, Jordi, Campdelacreu, Jaume, and Blesa, Rafael

Subjects
ATP-Binding Cassette, Early Onset Alzheimer’s disease, Loss-of-function, Member 7 (ABCA7), Modifier, RNA sequencing, Sub-Family A, Third-generation long-read sequencing, 2734, Neurology (clinical), Cellular and Molecular Neuroscience
Published
2017

42. TBK1 Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Author

van der Zee, Julie, Gijselinck, Ilse, Van Mossevelde, Sara, Perrone, Federica, Dillen, Lubina, Heeman, Bavo, Bäumer, Veerle, Engelborghs, Sebastiaan, De Bleecker, Jan, Baets, Jonathan, Gelpi, Ellen, Rojas García, Ricardo, Clarimon, Jordi, Lleó Bisa, Alberto, Diehl‐Schmid, Janine, Alexopoulos, Panagiotis, Perneczky, Robert, Synofzik, Matthis, Just, Jennifer, Schöls, Ludger, Graff, Caroline, Thonberg, Håkan, Borroni, Barbara, Padovani, Alessandro, Jordanova, Albena, Sarafov, Stayko, Tournev, Ivailo, de Mendonça, Alexandre, Miltenberger‐Miltényi, Gabriel, Simões do Couto, Frederico, Ramirez, Alfredo, Jessen, Frank, Heneka, Michael T., Gómez‐Tortosa, Estrella, Danek, Adrian, Cras, Patrick, Vandenberghe, Rik, De Jonghe, Peter, De Deyn, Peter P., Sleegers, Kristel, Cruts, Marc, Van Broeckhoven, Christine, Goeman, Johan, Nuytten, Dirk, Smets, Katrien, Robberecht, Wim, Damme, Philip Van, Bleecker, Jan De, Santens, Patrick, Dermaut, Bart, Versijpt, Jan, Michotte, Alex, Ivanoiu, Adrian, Deryck, Olivier, Bergmans, Bruno, Delbeck, Jean, Bruyland, Marc, Willems, Christiana, Salmon, Eric, Pastor, Pau, Ortega‐Cubero, Sara, Benussi, Luisa, Ghidoni, Roberta, Binetti, Giuliano, Hernández, Isabel, Boada Rovira, Mercè, Ruiz Laza, Agustín, Sorbi, Sandro, Nacmias, Benedetta, Bagnoli, Silvia, Sánchez Valle, Raquel, Lladó, Albert, Santana, Isabel, Rosário Almeida, Maria, Frisoni, Giovanni B, Maetzler, Walter, Matej, Radoslav, Fraidakis, Matthew J., Kovacs, Gabor G., Fabrizi, Gian Maria, Testi, Silvia, van der Zee, Julie, Gijselinck, Ilse, Van Mossevelde, Sara, Perrone, Federica, Dillen, Lubina, Heeman, Bavo, Bäumer, Veerle, Engelborghs, Sebastiaan, De Bleecker, Jan, Baets, Jonathan, Gelpi, Ellen, Rojas García, Ricardo, Clarimon, Jordi, Lleó Bisa, Alberto, Diehl‐Schmid, Janine, Alexopoulos, Panagiotis, Perneczky, Robert, Synofzik, Matthis, Just, Jennifer, Schöls, Ludger, Graff, Caroline, Thonberg, Håkan, Borroni, Barbara, Padovani, Alessandro, Jordanova, Albena, Sarafov, Stayko, Tournev, Ivailo, de Mendonça, Alexandre, Miltenberger‐Miltényi, Gabriel, Simões do Couto, Frederico, Ramirez, Alfredo, Jessen, Frank, Heneka, Michael T., Gómez‐Tortosa, Estrella, Danek, Adrian, Cras, Patrick, Vandenberghe, Rik, De Jonghe, Peter, De Deyn, Peter P., Sleegers, Kristel, Cruts, Marc, Van Broeckhoven, Christine, Goeman, Johan, Nuytten, Dirk, Smets, Katrien, Robberecht, Wim, Damme, Philip Van, Bleecker, Jan De, Santens, Patrick, Dermaut, Bart, Versijpt, Jan, Michotte, Alex, Ivanoiu, Adrian, Deryck, Olivier, Bergmans, Bruno, Delbeck, Jean, Bruyland, Marc, Willems, Christiana, Salmon, Eric, Pastor, Pau, Ortega‐Cubero, Sara, Benussi, Luisa, Ghidoni, Roberta, Binetti, Giuliano, Hernández, Isabel, Boada Rovira, Mercè, Ruiz Laza, Agustín, Sorbi, Sandro, Nacmias, Benedetta, Bagnoli, Silvia, Sánchez Valle, Raquel, Lladó, Albert, Santana, Isabel, Rosário Almeida, Maria, Frisoni, Giovanni B, Maetzler, Walter, Matej, Radoslav, Fraidakis, Matthew J., Kovacs, Gabor G., Fabrizi, Gian Maria, and Testi, Silvia

Abstract

We investigated the mutation spectrum of the TANK‐Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early‐Onset Dementia Consortium. We assessed pathogenicity of predicted protein‐truncating mutations by measuring loss of RNA expression. Functional effect of in‐frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB‐induced luciferase reporter assay and measuring phosphorylated TBK1. The protein‐truncating mutations led to the loss of transcript through nonsense‐mediated mRNA decay. For the in‐frame amino acid deletions, we demonstrated loss of TBK1 or phosphorylated TBK1 protein. An important fraction of the missense mutations compromised NFκB activation indicating that at least some functions of TBK1 are lost. Although missense mutations were also present in controls, over three times more mutations affecting TBK1 functioning were found in the mutation fraction observed in patients only, suggesting high‐risk alleles (P = 0.03). Total mutation frequency for confirmed TBK1 LoF mutations in the European cohort was 0.7%, with frequencies in the clinical subgroups of 0.4% in FTD, 1.3% in ALS, and 3.6% in FTD‐ALS.

Published
2017

43. TBK1Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Author

UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, van der Zee, Julie, Gijselinck, Ilse, Van Mossevelde, Sara, Perrone, Federica, Dillen, Lubina, Heeman, Bavo, Bâumer, Veerle, Engelborghs, Sebastiaan, De Bleecker, Jan, Baets, Jonathan, Gelpi, Ellen, Rojas-García, Ricardo, Clarimón, Jordi, Lleó, Alberto, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Perneczky, Robert, Synofzik, Matthis, Just, Jennifer, Schöls, Ludger, Graff, Caroline, Thonberg, Hakan, Borroni, Barbara, Padovani, Alessandro, Jordanova, Albena, Sarafov, Stayko, Tournev, Ivailo, de Mendonça, Alexandre, Miltenberger-Miltényi, Gabriel, Simões do Couto, Frederico, Ramirez, Alfredo, Jessen, Frank, Heneka, Michael T., Gómez-Tortosa, Estrella, Danek, Adrian, Cras, Patrick, Vandenberghe, Rik, De Jonghe, Peter, De Deyn, Peter P., Sleegers, Kristel, Cruts, Marc, Van Broeckhoven, Christine, Goeman, Johan, Nuytten, Dirk, Smets, Katrien, Robberecht, Wim, Damme, Philip Van, Bleecker, Jan De, Santens, Patrick, Dermaut, Bart, Versijpt, Jan, Michotte, Alex, Ivanoiu, Adrian, Deryck, Olivier, Bergmans, Bruno, Delbeck, Jean, Bruyland, Marc, Willems, Christiana, Salmon, Eric, Pastor, Pau, Ortega-Cubero, Sara, Benussi, Luisa, Ghidoni, Roberta, Binetti, Giuliano, Hernàndez, Isabel, Boada, Mercè, Ruiz, Agustín, Sorbi, Sandro, Nacmias, Benedetta, Bagnoli, Silvia, Sanchez-Valle, Raquel, Llado, Albert, Santana, Isabel, Rosàrio Almeida, Maria, Frisoni, Giovanni B, Maetzler, Walter, Matej, Radoslav, Fraidakis, Matthew J., Kovacs, Gabor G., Fabrizi, Gian Maria, Testi, Silvia, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, van der Zee, Julie, Gijselinck, Ilse, Van Mossevelde, Sara, Perrone, Federica, Dillen, Lubina, Heeman, Bavo, Bâumer, Veerle, Engelborghs, Sebastiaan, De Bleecker, Jan, Baets, Jonathan, Gelpi, Ellen, Rojas-García, Ricardo, Clarimón, Jordi, Lleó, Alberto, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Perneczky, Robert, Synofzik, Matthis, Just, Jennifer, Schöls, Ludger, Graff, Caroline, Thonberg, Hakan, Borroni, Barbara, Padovani, Alessandro, Jordanova, Albena, Sarafov, Stayko, Tournev, Ivailo, de Mendonça, Alexandre, Miltenberger-Miltényi, Gabriel, Simões do Couto, Frederico, Ramirez, Alfredo, Jessen, Frank, Heneka, Michael T., Gómez-Tortosa, Estrella, Danek, Adrian, Cras, Patrick, Vandenberghe, Rik, De Jonghe, Peter, De Deyn, Peter P., Sleegers, Kristel, Cruts, Marc, Van Broeckhoven, Christine, Goeman, Johan, Nuytten, Dirk, Smets, Katrien, Robberecht, Wim, Damme, Philip Van, Bleecker, Jan De, Santens, Patrick, Dermaut, Bart, Versijpt, Jan, Michotte, Alex, Ivanoiu, Adrian, Deryck, Olivier, Bergmans, Bruno, Delbeck, Jean, Bruyland, Marc, Willems, Christiana, Salmon, Eric, Pastor, Pau, Ortega-Cubero, Sara, Benussi, Luisa, Ghidoni, Roberta, Binetti, Giuliano, Hernàndez, Isabel, Boada, Mercè, Ruiz, Agustín, Sorbi, Sandro, Nacmias, Benedetta, Bagnoli, Silvia, Sanchez-Valle, Raquel, Llado, Albert, Santana, Isabel, Rosàrio Almeida, Maria, Frisoni, Giovanni B, Maetzler, Walter, Matej, Radoslav, Fraidakis, Matthew J., Kovacs, Gabor G., Fabrizi, Gian Maria, and Testi, Silvia

Abstract

We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1. The protein-truncating mutations led to the loss of transcript through nonsense-mediated mRNA decay. For the in-frame amino acid deletions, we demonstrated loss of TBK1 or phosphorylated TBK1 protein. An important fraction of the missense mutations compromised NFκB activation indicating that at least some functions of TBK1 are lost. Although missense mutations were also present in controls, over three times more mutations affecting TBK1 functioning were found in the mutation fraction observed in patients only, suggesting high-risk alleles (P = 0.03). Total mutation frequency for confirmed TBK1 LoF mutations in the European cohort was 0.7%, with frequencies in the clinical subgroups of 0.4% in FTD, 1.3% in ALS, and 3.6% in FTD-ALS.

Published
2017

44. Effects of Multiple Genetic Loci on Age at Onset in Frontotemporal Dementia

Author

Ferrari, R, Grassi, M, Graziano, F, Palluzzi, F, Archetti, S, Bonomi, E, Bruni, A, Maletta, R, Bernardi, L, Cupidi, C, Colao, R, Rainero, I, Rubino, E, Pinessi, L, Galimberti, D, Scarpini, E, Serpente, M, Nacmias, B, Piaceri, I, Bagnoli, S, Rossi, G, Giaccone, G, Tagliavini, F, Benussi, L, Binetti, G, Ghidoni, R, Singleton, A, Hardy, J, Momeni, P, Padovani, A, Borroni, B, Ferrari, Raffaele, Grassi, Mario, Graziano, Francesca, Palluzzi, Fernando, Archetti, Silvana, Bonomi, Elisa, Bruni, Amalia C., Maletta, Raffaele G., Bernardi, Livia, Cupidi, Chiara, Colao, Rosanna, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Galimberti, Daniela, Scarpini, Elio, Serpente, Maria, Nacmias, Benedetta, Piaceri, Irene, Bagnoli, Silvia, Rossi, Giacomina, Giaccone, Giorgio, Tagliavini, Fabrizio, Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Singleton, Andrew, Hardy, John, Momeni, Parastoo, Padovani, Alessandro, Borroni, Barbara, Ferrari, R, Grassi, M, Graziano, F, Palluzzi, F, Archetti, S, Bonomi, E, Bruni, A, Maletta, R, Bernardi, L, Cupidi, C, Colao, R, Rainero, I, Rubino, E, Pinessi, L, Galimberti, D, Scarpini, E, Serpente, M, Nacmias, B, Piaceri, I, Bagnoli, S, Rossi, G, Giaccone, G, Tagliavini, F, Benussi, L, Binetti, G, Ghidoni, R, Singleton, A, Hardy, J, Momeni, P, Padovani, A, Borroni, B, Ferrari, Raffaele, Grassi, Mario, Graziano, Francesca, Palluzzi, Fernando, Archetti, Silvana, Bonomi, Elisa, Bruni, Amalia C., Maletta, Raffaele G., Bernardi, Livia, Cupidi, Chiara, Colao, Rosanna, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Galimberti, Daniela, Scarpini, Elio, Serpente, Maria, Nacmias, Benedetta, Piaceri, Irene, Bagnoli, Silvia, Rossi, Giacomina, Giaccone, Giorgio, Tagliavini, Fabrizio, Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Singleton, Andrew, Hardy, John, Momeni, Parastoo, Padovani, Alessandro, and Borroni, Barbara

Abstract

In frontotemporal dementia (FTD), age at disease onset (AAO) is unpredictable in both early and late-onset cases; AAO variability is found even in autosomal dominant FTD. The present study was aimed at identifying genetic modifiers modulating AAO in a large cohort of Italian FTD patients. We conducted an association analysis on 411 FTD patients, belonging to 7 Italian Centers, and for whom AAO was available. Population structure was evaluated by principal component analysis to infer continuous axes of genetic variation, and single linear regression models were applied. A genetic score (GS) was calculated on the basis of suggestive single nucleotide polymorphisms (SNPs) found by association analyses. GS showed genome-wide significant slope decrease by -3.86 (95 CI: -4.64 to -3.07, p<2×10 -16 ) per standard deviation of the GS for 6 SNPs mapping to genes involved in neuronal development and signaling, axonal myelinization, and glutamatergic/GABA neurotransmission. An increase of the GS was associated with a decrease of the AAO. Our data indicate that there is indeed a genetic component that underpins and modulates up to 14.5 of variability of AAO in Italian FTD. Future studies on genetic modifiers in FTD are warranted.

Published
2017

45. Notch4 and mhc class II polymorphisms are associated with hcv-related benign and malignant lymphoproliferative diseases

Author

Gragnani, Laura, primary, Fognani, Elisa, additional, De Re, Valli, additional, Libra, Massimo, additional, Garozzo, Adriana, additional, Caini, Patrizio, additional, Cerretelli, Guia, additional, Giovannelli, Andrea, additional, Lorini, Serena, additional, Monti, Monica, additional, Bagnoli, Silvia, additional, Piaceri, Irene, additional, and Zignego, Anna Linda, additional

Published
2017
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46. Fat mass and obesity-associated gene (FTO) is associated to eating disorders susceptibility and moderates the expression of psychopathological traits

Author

Castellini, Giovanni, primary, Franzago, Marica, additional, Bagnoli, Silvia, additional, Lelli, Lorenzo, additional, Balsamo, Michela, additional, Mancini, Milena, additional, Nacmias, Benedetta, additional, Ricca, Valdo, additional, Sorbi, Sandro, additional, Antonucci, Ivana, additional, Stuppia, Liborio, additional, and Stanghellini, Giovanni, additional

Published
2017
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47. A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia

Author

Ferrari, Raffaele, Grassi, Mario, Salvi, Erika, Borroni, Barbara, Palluzzi, Fernando, Pepe, Daniele, D'Avila, Francesca, Padovani, Alessandro, Archetti, Silvana, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Galimberti, Daniela, Scarpini, Elio, Serpente, Maria, Rossi, Giacomina, Giaccone, Giorgio, Tagliavini, Fabrizio, Nacmias, Benedetta, Piaceri, Irene, Bagnoli, Silvia, Bruni, Amalia C., Maletta, Raffaele G., Bernardi, Livia, Postiglione, Alfredo, Milan, Graziella, Franceschi, Massimo, Puca, Annibale A., Novelli, Valeria, Barlassina, Cristina, Glorioso, Nicola, Manunta, Paolo, Singleton, Andrew, Cusi, Daniele, Hardy, John, Momeni, Parastoo, Ferrari, R, Grassi, M, Salvi, E, Borroni, B, Palluzzi, F, Pepe, D, D’Avila, F, Padovani, A, Archetti, S, Rainero, I, Rubino, E, Pinessi, L, Benussi, L, Binetti, G, Ghidoni, R, Galimberti, D, Scarpini, E, Serpente, M, Rossi, G, Giaccone, G, Tagliavini, F, Nacmias, B, Piaceri, I, Bagnoli, S, Bruni, Ac, Maletta, Rg, Bernardi, L, Postiglione, A, Milan, G, Franceschi, M, Puca, Aa, Novelli, V, Barlassina, C, Glorioso, N, Manunta, Paolo, Singleton, A, Cusi, D, Hardy, J, and Momeni, P.

Subjects
Male, Aging, Neurogenesis, Neuroscience(all), Population, Clinical Neurology, Polymorphism, Single Nucleotide, Cohort Studies, Risk Factors, mental disorders, Humans, Genetic Report Abstract, Alleles, Aged, Aged, 80 and over, Neurons, Neuroscience (all), Brain, Cell Differentiation, Functional annotation, Middle Aged, Protein-Tyrosine Kinases, Case-control, Association study, Frontotemporal dementia, Genetic risk factors, Axons, Ageing, Haplotypes, Glucosyltransferases, Case-Control Studies, Intercellular Signaling Peptides and Proteins, Female, Neurology (clinical), Geriatrics and Gerontology, Apoptosis Regulatory Proteins, Developmental Biology, Genome-Wide Association Study
Abstract

Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD. Suggestive SNPs reached p-values ∼10−7 and odds ratio > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of –cis genes such as RFNG and AATK involved in neuronal genesis and differentiation and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation, and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD–genome-wide association study. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis.

Published
2015

48. Monomeric ß-amyloid interacts with type-1 insulin-like growth factor receptors to provide energy supply to neurons

Author

Giuffrida, Maria L, Tomasello, Marianna F., Pandini, Giuseppe, Caraci, Filippo, Battaglia, Giuseppe, Busceti, Carla, Di Pietro, Paola, Pappalardo, Giuseppe, Attanasio, Francesco, Chiechio, Santina, Bagnoli, Silvia, Nacmias, Benedetta, Sorbi, Sandro, Vigneri, Riccardo, Rizzarelli, Enrico, Nicoletti, Ferdinando, and Copani, Agata

Subjects
Alzheimer’s disease, Glucose, Glut3, IGF-IR, ß-amyloid, Cellular and Molecular Neuroscience
Published
2015

50. Monomeric ß-amyloid interacts with type-1 insulin-like growth factor receptors to provide energy supply to neurons

Author

Giuffrida, Maria L., primary, Tomasello, Marianna F., additional, Pandini, Giuseppe, additional, Caraci, Filippo, additional, Battaglia, Giuseppe, additional, Busceti, Carla, additional, Di Pietro, Paola, additional, Pappalardo, Giuseppe, additional, Attanasio, Francesco, additional, Chiechio, Santina, additional, Bagnoli, Silvia, additional, Nacmias, Benedetta, additional, Sorbi, Sandro, additional, Vigneri, Riccardo, additional, Rizzarelli, Enrico, additional, Nicoletti, Ferdinando, additional, and Copani, Agata, additional

Published
2015
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