1. Association of Rare APOE Missense Variants V236E and R251G with Risk of Alzheimer Disease
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Le Guen, Yann, Belloy, Michael E, Eger, Sarah J, Mir, Pablo, Moreno, Fermin, Pastor, Pau, Piñol-Ripoll, Gerard, Molina-Porcel, Laura, Pérez-Tur, Jordi, Rodríguez-Rodríguez, Eloy, Royo, Jose Luís, Sánchez-Valle, Raquel, Dichgans, Martin, Rasmussen, Katrine Laura, Rujescu, Dan, Thomassen, Jesper Qvist, Deleuze, Jean-François, He, Zihuai, Napolioni, Valerio, Amouyel, Philippe, Jessen, Frank, Kehoe, Patrick Gavin, van Duijn, Cornelia, Grenier-Boley, Benjamin, Tsolaki, Magda, Sánchez-Juan, Pascual, Sleegers, Kristel, Ingelsson, Martin, Rossi, Giacomina, Hiltunen, Mikko, Sims, Rebecca, van der Flier, Wiesje M, Ramirez, Alfredo, Andreassen, Ole A, de Rojas, Itziar, Frikke-Schmidt, Ruth, Williams, Julie, Ruiz, Agustín, Lambert, Jean-Charles, Greicius, Michael D, Members of the EADB, GR@ACE, DEGESCO, DemGene, GERAD, Groups, EADI, Arosio, Beatrice, Benussi, Luisa, Boland, Anne, Castillo-Morales, Atahualpa, Borroni, Barbara, Caffarra, Paolo, Daian, Delphine, Daniele, Antonio, Debette, Stéphanie, Dufouil, Carole, Düzel, Emrah, Galimberti, Daniela, Giedraitis, Vilmantas, Grimmer, Timo, Jansen, Iris, Graff, Caroline, Grünblatt, Edna, Hanon, Olivier, Hausner, Lucrezia, Heilmann-Heimbach, Stefanie, Holstege, Henne, Hort, Jakub, Jürgen, Deckert, Kuulasmaa, Teemu, van der Lugt, Aad, Nicolas, Aude, Masullo, Carlo, Mecocci, Patrizia, Mehrabian, Shima, de Mendonça, Alexandre, Moebus, Susanne, Nacmias, Benedetta, Nicolas, Gael, Olaso, Robert, Papenberg, Goran, Parnetti, Lucilla, Bellenguez, Céline, Pasquier, Florence, Peters, Oliver, Pijnenburg, Yolande A L, Popp, Julius, Rainero, Innocenzo, Ramakers, Inez, Riedel-Heller, Steffi, Scarmeas, Nikolaos, Scheltens, Philip, Scherbaum, Norbert, Dalmasso, Carolina, Schneider, Anja, Seripa, Davide, Soininen, Hilkka, Solfrizzi, Vincenzo, Spalletta, Gianfranco, Squassina, Alessio, van Swieten, John, Tegos, Thomas J, Tremolizzo, Lucio, Verhey, Frans, Küçükali, Fahri, Vyhnalek, Martin, Wiltfang, Jens, Boada, Mercè, García-González, Pablo, Puerta, Raquel, Real, Luis M, Álvarez, Victoria, Bullido, María J, Clarimon, Jordi, García-Alberca, José María, Neurology, Amsterdam Neuroscience - Neurodegeneration, VU University medical center, APH - Personalized Medicine, APH - Methodology, National Institutes of Health (US), National Institute on Aging (US), European Research Council, Pérez-Tur, Jordi [0000-0002-9111-1712], RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychology 2, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), Le Guen, Y, Belloy, M, Grenier-Boley, B, de Rojas, I, Castillo-Morales, A, Jansen, I, Nicolas, A, Bellenguez, C, Dalmasso, C, Küçükali, F, Eger, S, Rasmussen, K, Thomassen, J, Deleuze, J, He, Z, Napolioni, V, Amouyel, P, Jessen, F, Kehoe, P, van Duijn, C, Tsolaki, M, Sánchez-Juan, P, Sleegers, K, Ingelsson, M, Rossi, G, Hiltunen, M, Sims, R, van der Flier, W, Ramirez, A, Andreassen, O, Frikke-Schmidt, R, Williams, J, Ruiz, A, Lambert, J, Greicius, M, Arosio, B, Benussi, L, Boland, A, Borroni, B, Caffarra, P, Daian, D, Daniele, A, Debette, S, Dufouil, C, Düzel, E, Galimberti, D, Giedraitis, V, Grimmer, T, Graff, C, Grünblatt, E, Hanon, O, Hausner, L, Heilmann-Heimbach, S, Holstege, H, Hort, J, Jürgen, D, Kuulasmaa, T, van der Lugt, A, Masullo, C, Mecocci, P, Mehrabian, S, de Mendonça, A, Moebus, S, Nacmias, B, Nicolas, G, Olaso, R, Papenberg, G, Parnetti, L, Pasquier, F, Peters, O, Pijnenburg, Y, Popp, J, Rainero, I, Ramakers, I, Riedel-Heller, S, Scarmeas, N, Scheltens, P, Scherbaum, N, Schneider, A, Seripa, D, Soininen, H, Solfrizzi, V, Spalletta, G, Squassina, A, van Swieten, J, Tegos, T, Tremolizzo, L, Verhey, F, Vyhnalek, M, Wiltfang, J, Boada, M, García-González, P, Puerta, R, Real, L, Álvarez, V, Bullido, M, Clarimon, J, García-Alberca, J, Mir, P, Moreno, F, Pastor, P, Piñol-Ripoll, G, Molina-Porcel, L, Pérez-Tur, J, Rodríguez-Rodríguez, E, Royo, J, Sánchez-Valle, R, Dichgans, M, Rujescu, D, Epidemiology, Radiology & Nuclear Medicine, Graduate School, Medical Psychology, APH - Quality of Care, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), EADB Group, GR@ACE Groupp, DEGESCO Group, DemGene Group, GERAD Group, EADI Group, Repositório da Universidade de Lisboa, and Pérez-Tur, Jordi
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Male ,Genotype ,Apolipoprotein E2 ,epidemiology [Alzheimer Disease] ,Apolipoprotein E4 ,Medizin ,genetics [Alzheimer Disease] ,APOLIPOPROTEIN-E ,Apolipoproteins E ,Settore BIO/13 - Biologia Applicata ,Alzheimer Disease ,genetics [Apolipoprotein E2] ,Humans ,BEHAVIORAL DEFICITS ,ddc:610 ,Age of Onset ,PROGRESS ,Alleles ,genetics [Apolipoprotein E4] ,Alzheimer's disease, genetics, APOE, risk factor ,A-BETA ,Original Investigation ,Settore MED/26 - NEUROLOGIA ,ALLELE ,genetics [Apolipoproteins E] ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Female ,INFERENCE ,Neurology (clinical) ,Human medicine - Abstract
34 páginas, 2 tablas, 2 figuras. 2 ficheros con material suplementario. Data used in preparation of this manuscript can be obtained upon application at: - dbGaP (https://www.ncbi.nlm.nih.gov/gap/advanced_search/) - NIAGADS and NIAGADS DSS (https://www.niagads.org/) - LONI (https://ida.loni.usc.edu/) - Synapse (https://adknowledgeportal.synapse.org/) - RADC Rush (https://www.radc.rush.edu/) - NACC (https://naccdata.org/) - UK Biobank (https://biobank.ndph.ox.ac.uk/showcase/), The APOE ε2 and APOE ε4 alleles are the strongest protective and risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, the mechanisms linking APOE to AD-particularly the apoE protein's role in AD pathogenesis and how this is affected by APOE variants-remain poorly understood. Identifying missense variants in addition to APOE ε2 and APOE ε4 could provide critical new insights, but given the low frequency of additional missense variants, AD genetic cohorts have previously been too small to interrogate this question robustly., This work was supported by the National Institute of Health and National Institute of Aging grants AG060747 (MDG), AG066206 (ZH), AG066515 (ZH, MDG), the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie (grant agreement No. 890650, YLG), the Alzheimer’s Association (AARF-20-683984, MEB), and the Iqbal Farrukh and Asad Jamal Fund, a grant from the EU Joint Programme – Neurodegenerative Disease Research (European Alzheimer DNA BioBank, EADB; JPND). Inserm UMR1167 is also funded by the Inserm, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine, and the French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to Alzheimer’s disease). EADB thank the study participants, researchers, and staff for collecting and contributing to the data, the high-performance computing service at the University of Lille, and the staff at CEA-CNRGH for their help with sample preparation and genotyping, and technical assistance. Additional funders of individual investigators and institutions who contributed to data collection and genotyping are provided in the Supplemental Online Content.
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- 2022