Letter | Published:

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

Nature Genetics volume 49, pages 13731384 (2017) | Download Citation

Abstract

We identified rare coding variants associated with Alzheimer's disease in a three-stage case–control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10−4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10−8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10−10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10−10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10−14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein–protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

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Acknowledgements

GERAD/PERADES. We thank all individuals who participated in this study. Cardiff University was supported by the Alzheimer's Society (AS; grant RF014/164) and the Medical Research Council (MRC; grants G0801418/1, MR/K013041/1, MR/L023784/1) (R. Sims is an AS Research Fellow). Cardiff University was also supported by the European Joint Programme for Neurodegenerative Disease (JPND; grant MR/L501517/1), Alzheimer's Research UK (ARUK; grant ARUK-PG2014-1), the Welsh Assembly Government (grant SGR544:CADR), and a donation from the Moondance Charitable Foundation. Cardiff University acknowledges the support of the UK Dementia Research Institute, of which J. Williams is an associate director. Cambridge University acknowledges support from the MRC. Patient recruitment for the MRC Prion Unit/UCL Department of Neurodegenerative Disease collection was supported by the UCLH/UCL Biomedical Centre and NIHR Queen Square Dementia Biomedical Research Unit. The University of Southampton acknowledges support from the AS. King's College London was supported by the NIHR Biomedical Research Centre for Mental Health and the Biomedical Research Unit for Dementia at the South London and Maudsley NHS Foundation Trust and by King's College London and the MRC. ARUK and the Big Lottery Fund provided support to Nottingham University. Ulster Garden Villages, AS, ARUK, the American Federation for Aging Research, and the Northern Ireland R&D Office provided support for Queen's University, Belfast. The Centro de Biología Molecular Severo Ochoa (CSIS-UAM), CIBERNED, Instituto de Investigación Sanitaria la Paz, University Hospital La Paz, and the Universidad Autónoma de Madrid were supported by grants from the Ministerio de Educación y Ciencia and the Ministerio de Sanidad y Consumo (Instituto de Salud Carlos III) and by an institutional grant of the Fundación Ramón Areces to the CMBSO. We thank I. Sastre and A. Martinez-Garcia for DNA preparation, and P. Gil and P. Coria for their recruitment efforts. The Department of Neurology, University Hospital Mútua de Terrassa, was supported by CIBERNED, Instituto de Salud Carlos III, Madrid, Spain, and acknowledges M.A. Pastor (University of Navarra Medical School and Center for Applied Medical Research), M. Seijo-Martinez (Hospital do Salnes), and R. Rene, J. Gascon, and J. Campdelacreu (Hospital de Bellvitage) for providing DNA samples. The Hospital de la Sant Pau, Universitat Autònoma de Barcelona, acknowledges support from the Spanish Ministry of Economy and Competitiveness (grant PI12/01311) and from the Generalitat de Catalunya (2014SGR-235). The Santa Lucia Foundation and the Fondazione Ca' Granda IRCCS Ospedale Policlinico, Italy, acknowledge the Italian Ministry of Health (grant RC 10.11.12.13/A). The Bonn samples are part of the German Dementia Competence Network (DCN) and the German Research Network on Degenerative Dementia (KNDD), which are funded by the German Federal Ministry of Education and Research (grants KND: 01G10102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 04GI0434; grants KNDD: 01GI1007A, 01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716, 01ET1006B). M.M.N. is a member of the German Research Foundation (DFG) cluster of excellence ImmunoSensation. Funding for Saarland University was provided by the German Federal Ministry of Education and Research (BMBF), grant 01GS08125, to M. Riemenschneider. The University of Washington was supported by grants from the US National Institutes of Health (R01-NS085419 and R01-AG044546), the Alzheimer's Association (NIRG-11-200110), and the American Federation for Aging Research (C. Cruchaga was recipient of a New Investigator Award in Alzheimer's disease). Brigham Young University was supported by the Alzheimer's Association (MNIRG-11-205368), the BYU Gerontology Program, and the US National Institutes of Health (R01-AG11380, R01-AG021136, P30-S069329-01, R01-AG042611). We also acknowledge funding from the Institute of Neurology, UCL, London, who was supported in part by ARUK via an anonymous donor, and by a fellowship to R.G. The participation of D.S., M.U., and C. Masullo in the study was completely supported by Ministero della Salute, IRCCS Research Program, Ricerca Corrente 2015–2017, Linea 2 'Malattiecomplesse e Terapie Innovative' and by the '5 × 1000' voluntary contribution. AddNeuromed is supported by InnoMed, an Integrated Project funded by the European Union's Sixth Framework Programme priority FP6-2004-LIFESCIHEALTH-5, Life Sciences, Genomics, and Biotechnology for Health. We are grateful to the Wellcome Trust for awarding a Principal Research Fellowship to D.C.R. (095317/Z/11/Z). M. Riemenschneider was funded by BMBF NGFN grant 01GS08125. B.N. was supported by the Fondazione Cassa di Risparmio di Pistoia e Pescia (grants 2014.0365, 2011.0264, 2013.0347). H. Hampel is supported by the AXA Research Fund, the Fondation Universite Pierre et Marie Curie, and the 'Fondation pour la Recherche sur Alzheimer', Paris, France. The research leading to these results has received funding from the program 'Investissements d'Avenir', ANR-10-IAIHU-06 (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6.

CHARGE. Infrastructure for the CHARGE Consortium is supported in part by National Heart, Lung, and Blood Institute grant HL105756 and for the neurology working group by AG033193 and AG049505.

Rotterdam (RS). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study, and the participating general practitioners and pharmacists. Generation and management of the Illumina exome chip v1.0 array data for the Rotterdam Study (RS-I) was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine (http://www.glimdna.org/), Erasmus MC, Rotterdam, the Netherlands. The Exome chip array data set was funded by the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, from the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO)-sponsored Netherlands Consortium for Healthy Aging (NCHA; project 050-060-810); the Netherlands Organization for Scientific Research (NWO; project 184021007); and by the Rainbow Project (RP10; Netherlands Exome Chip Project) of Biobanking and Biomolecular Research Infrastructure Netherlands (BBMRI-NL; http://www.bbmri.nl). Generation and management of GWAS genotype data for the Rotterdam Study (RS-I, RS-II, RS-III) was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands. The GWAS data sets are supported by the Netherlands Organization of Scientific Research NWO Investments (175.010.2005.011, 911-03-012), the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), and the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA), project 050-060-810. This study makes use of an extended data set of RS-II and RS-III samples based on Illumina Omni 2.5 and 5.0 GWAS genotype data. This data set was funded by the Genetic Laboratory of the Department of Internal Medicine, the Department of Forensic Molecular Biology, and the Department of Dermatology, Erasmus MC, Rotterdam, the Netherlands. We thank M. Jhamai, S. Higgins, and M. Verkerk for their help in creating the exome chip database; C. Medina-Gomez, L. Karsten, and L. Broer for quality control and variant calling; M. Jhamai, M. Verkerk, L. Herrera, M. Peters, and C. Medina-Gomez for their help in creating the GWAS database; and L. Broer for the creation of the HRC-imputed data. Variants were called using the best practice protocol developed by M.L. Grove and colleagues as part of the CHARGE Consortium Exome Chip central calling effort. The work for this manuscript was further supported by ADAPTED: Alzheimer's Disease Apolipoprotein Pathology for Treatment Elucidation and Development (115975); the CoSTREAM project (http://www.costream.eu/); and funding from the European Union's Horizon 2020 research and innovation programme under grant agreement 667375.

AGES. The AGES study has been funded by NIA contracts N01-AG-12100 and HHSN271201200022C with contributions from NEI, NIDCD, and NHLBI, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament).

Cardiovascular Health Study (CHS). This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grant U01HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG033193, R01AG023629, R01AG15928, and R01AG20098 and by U01AG049505 from the National Institute on Aging (NIA). The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. A full list of CHS principal investigators and institutions can be found at https://chs-nhlbi.org/. The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health.

Framingham Heart Study. This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contracts N01-HC-25195 and HHSN268201500001I). This study was also supported by grants from the National Institute on Aging: AG033193, U01-AG049505, and AG008122 (S. Seshadri). S. Seshadri and A.L.D. were also supported by additional grants from the National Institute on Aging (R01AG049607) and the National Institute of Neurological Disorders and Stroke (R01-NS017950).

Fundació ACE. We sincerely acknowledge the collaboration of S. Ruiz, M. Rosende-Roca, A. Mauleon, L. Vargas, O. Rodriguez-Gomez, M. Alegret, A. Espinosa, G. Ortega, M. Tarragona, C. Abdelnour, and D. Sanchez. We thank all patients for their participation in this project. We are obliged to T. Port-Carbo and her family for their support of the Fundació ACE research programs. Fundació ACE collaborates with CIBERNED and is one of the participating centers of Dementia Genetics Spanish Consortium 430 (DEGESCO). CIBERNED is an Instituto de Salud Carlos III Project. A. Ruiz is supported by grant PI13/02434 (Acción Estratégica en Salud, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spain) and Obra Social 'La Caixa' (Barcelona, Spain).

ADGC. The US National Institutes of Health, National Institute on Aging (NIH-NIA) supported this work through the following grants: ADGC, U01 AG032984, and RC2 AG036528. Samples from the National Cell Repository for Alzheimer's Disease (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study. We thank the contributors who collected samples used in this study, as well as the patients and their families, whose help and participation made this work possible. Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689-01), NACC (U01 AG016976), NIA LOAD (Columbia University) (U24 AG026395, R01AG041797), Banner Sun Health Research Institute (P30 AG019610), Boston University (P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01 AG048927, R01AG33193), Columbia University (P50 AG008702, R37 AG015473), Duke University (P30 AG028377, AG05128), Emory University (AG025688), Group Health Research Institute (UO1 AG006781, UO1 HG004610, UO1 HG006375), Indiana University (P30 AG10133), Johns Hopkins University (P50 AG005146, R01 AG020688), Massachusetts General Hospital (P50 AG005134), Mayo Clinic (P50 AG016574), Mount Sinai School of Medicine (P50 AG005138, P01 AG002219), New York University (P30 AG08051, UL1 RR029893, 5R01AG012101, 5R01AG022374, 5R01AG013616, 1RC2AG036502, 1R01AG035137), Northwestern University (P30 AG013854), Oregon Health & Science University (P30 AG008017, R01 AG026916), Rush University (P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146), TGen (R01 NS059873), University of Alabama at Birmingham (P50 AG016582), University of Arizona (R01 AG031581), University of California, Davis (P30 AG010129), University of California, Irvine (P50 AG016573), University of California, Los Angeles (P50 AG016570), University of California, San Diego (P50 AG005131), University of California, San Francisco (P50 AG023501, P01 AG019724), University of Kentucky (P30 AG028383, AG05144), University of Michigan (P50 AG008671), University of Pennsylvania (P30 AG010124), University of Pittsburgh (P50 AG005133, AG030653, AG041718, AG07562, AG02365), University of Southern California (P50 AG005142), University of Texas Southwestern (P30 AG012300), University of Miami (R01 AG027944, AG010491, AG027944, AG021547, AG019757), University of Washington (P50 AG005136), University of Wisconsin (P50 AG033514), Vanderbilt University (R01 AG019085), and Washington University (P50 AG005681, P01 AG03991). The Kathleen Price Bryan Brain Bank at Duke University Medical Center is funded by NINDS grant NS39764, NIMH MH60451, and by GlaxoSmithKline. Support was also provided by the Alzheimer's Association (L.A.F., IIRG-08-89720; M.P.-V., IIRG-05-14147), the US Department of Veterans Affairs Administration, the Office of Research and Development, the Biomedical Laboratory Research Program, and the BrightFocus Foundation (M.P.-V., A2111048). P.S.G.-H. is supported by the Wellcome Trust, the Howard Hughes Medical Institute, and the Canadian Institutes of Health Research. Genotyping of the TGEN2 cohort was supported by Kronos Science. The TGen series was also funded by NIA grant AG041232 to A.J.M. and M.J.H., the Banner Alzheimer's Foundation, the Johnnie B. Byrd Sr. Alzheimer's Institute, the Medical Research Council, and the state of Arizona and also includes samples from the following sites: the Newcastle Brain Tissue Resource (funding via the Medical Research Council, local NHS trusts, and Newcastle University), the MRC London Brain Bank for Neurodegenerative Diseases (funding via the Medical Research Council), the South West Dementia Brain Bank (funding via numerous sources including the Higher Education Funding Council for England (HEFCE), Alzheimer's Research UK (ARUK), and BRACE as well as the North Bristol NHS Trust Research and Innovation Department and DeNDRoN), the Netherlands Brain Bank (funding via numerous sources including Stichting MS Research, Brain Net Europe, Hersenstichting Nederland Breinbrekend Werk, International Parkinson Fonds, Internationale Stiching Alzheimer Onderzoek), and the Institut de Neuropatologia, Servei Anatomia Patologica, Universitat de Barcelona. ADNI data collection and sharing were funded by US National Institutes of Health grant U01 AG024904 and Department of Defense award W81XWH-12-2-0012. ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; the Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai, Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche, Ltd., and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO, Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development, LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer, Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research provide funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (http://www.fnih.org/). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. We thank D.S. Snyder and M. Miller from the NIA who are ex-officio ADGC members.

EADI. This work was supported by INSERM, the National Foundation for Alzheimer's Disease and Related Disorders, the Institut Pasteur de Lille, and the Centre National de Génotypage. This work has been developed and supported by the LABEX (Laboratory of Excellence Program Investment for the Future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer's Disease) including funding from MEL (Métropole Européenne de Lille), ERDF (European Regional Development Fund), and the Conseil Régional du Nord-Pas-de-Calais. The Three-City Study was performed as part of collaboration between INSERM, Victor Segalen Bordeaux II University, and Sanofi-Synthelabo. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also funded by the Caisse Nationale Maladie des Travailleurs Salaries, Direction Générale de la Santé, MGEN, Institut de la Longévité, Agence Française de Sécurité Sanitaire des Produits de Santé, the Aquitaine and Bourgogne regional councils, Agence Nationale de la Recherche (ANR supported the COGINUT and COVADIS projects), Fondation de France, and the joint French Ministry of Research/INSERM 'Cohortes et Collections de Données Biologiques' program. The Lille Genopole received an unconditional grant from Eisai and was supported by the European Joint Programme for Neurodegenerative Disease (JPND: grant MR/L501517/1). The Three-City Biological Bank was developed and maintained by the Laboratory for Genomic Analysis LAG-BRC, Institut Pasteur de Lille.

Belgium sample collection. Research at the Antwerp site is funded in part by the Interuniversity Attraction Poles program of the Belgian Science Policy Office, the Foundation for Alzheimer Research (SAO-FRA), a Methusalem Excellence Grant of the Flemish Government, the Research Foundation Flanders (FWO), and the Special Research Fund of the University of Antwerp, Belgium. Authors from the Antwerp site thank the personnel of the VIB Genetic Service Facility, the Biobank of the Institute Born-Bunge, and the Departments of Neurology and Memory Clinics at the Hospital Network Antwerp and University Hospitals Leuven.

Finnish sample collection. Financial support for this project was provided by the Health Research Council of the Academy of Finland, EVO grant 5772708 of Kuopio University Hospital, and the Nordic Center of Excellence in Neurodegeneration.

Swedish sample collection. Sample collection was financially supported in part by the Swedish Brain Power network, the Marianne and Marcus Wallenberg Foundation, the Swedish Research Council (521-2010-3134), King Gustaf V and Queen Victoria's Foundation of Freemasons, the Regional Agreement on Medical Training and Clinical Research (ALF) between the Stockholm County Council and the Karolinska Institutet, the Swedish Brain Foundation, and the Swedish Alzheimer Foundation.

AMP AD University of Florida/Mayo Clinic/Institutes of Systems Biology. For human brain donations, we thank all patients and their families, without whom this work would not have been possible. This work was supported by NIH/NIA AG046139-01 (T.E.G., N.E.-T., N.P., S.G.Y.). We thank T.G. Beach (Banner Sun Health Institute) for sharing human tissue.

The Mayo Clinic Brain Bank. Data collection was supported through funding by NIA grants P50 AG016574, R01 AG032990, U01 AG046139, R01 AG018023, U01 AG006576, U01 AG006786, R01 AG025711, R01 AG017216, and R01 AG003949, NINDS grant R01 NS080820, the CurePSP Foundation, and support from the Mayo Foundation.

Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona. The Brain and Body Donation Program is supported by the National Institute of Neurological Disorders and Stroke (U24 NS072026 National Brain and Tissue Resource for Parkinson's Disease and Related Disorders), the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901, and 1001 to the Arizona Parkinson's Disease Consortium), and the Michael J. Fox Foundation for Parkinson's Research.

Author information

Author notes

    • Rebecca Sims
    • , Sven J van der Lee
    • , Adam C Naj
    •  & Céline Bellenguez

    These authors contributed equally to this work.

    • Philippe Amouyel
    • , Cornelia M van Duijn
    • , Alfredo Ramirez
    • , Li-San Wang
    • , Jean-Charles Lambert
    • , Sudha Seshadri
    • , Julie Williams
    •  & Gerard D Schellenberg

    These authors jointly directed this work.

Affiliations

  1. Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.

    • Rebecca Sims
    • , Nandini Badarinarayan
    • , Rachel Raybould
    • , Maria Vronskaya
    • , Rhodri Thomas
    • , Taniesha Morgan
    • , Nicola Denning
    • , Elisa Majounie
    • , Melanie Dunstan
    • , Amy Braddel
    • , Charlene Thomas
    • , Alun Meggy
    • , Rachel Marshall
    • , Amy Gerrish
    • , Jade Chapman
    • , Sarah Taylor
    • , Matt Hill
    • , Michael C O'Donovan
    • , Michael J Owen
    • , Lesley Jones
    • , Valentina Escott-Price
    • , Peter A Holmans
    •  & Julie Williams
  2. Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.

    • Sven J van der Lee
    • , Shahzad Ahmad
    • , Frank J Wolters
    • , Hieab H Adams
    • , Albert Hofman
    • , Fernando Rivadeneira
    • , Andre G Uitterlinden
    • , M Arfan Ikram
    • , Najaf Amin
    •  & Cornelia M van Duijn
  3. Department of Biostatistics and Epidemiology/Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

    • Adam C Naj
  4. INSERM, U1167, RID-AGE–Risk Factors and Molecular Determinants of Aging-Related Diseases, Lille, France.

    • Céline Bellenguez
    • , Benjamin Grenier-Boley
    • , Nathalie Fievet
    • , Philippe Amouyel
    •  & Jean-Charles Lambert
  5. Institut Pasteur de Lille, Lille, France.

    • Céline Bellenguez
    • , Benjamin Grenier-Boley
    • , Nathalie Fievet
    • , Philippe Amouyel
    •  & Jean-Charles Lambert
  6. University Lille, U1167–Excellence Laboratory LabEx DISTALZ, Lille, France.

    • Céline Bellenguez
    • , Benjamin Grenier-Boley
    • , Nathalie Fievet
    • , Philippe Amouyel
    •  & Jean-Charles Lambert
  7. Icelandic Heart Association, Kopavogur, Iceland.

    • Johanna Jakobsdottir
    • , Albert V Smith
    • , Gudny Eiriksdottir
    • , Valur Emilsson
    • , Thor Aspelund
    •  & Vilmundur Gudnason
  8. John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA.

    • Brian W Kunkle
    • , Eden R Martin
    • , Kara L Hamilton-Nelson
    • , Gary W Beecham
    • , Patrice Whitehead
    • , John R Gilbert
    • , William Perry
    •  & Margaret A Pericak-Vance
  9. CEA/Institut de Génomique, Centre National de Génotypage, Evry, France.

    • Anne Boland
    • , Robert Olaso
    • , Cécile Dulary
    • , Céline Derbois
    • , Delphine Bacq
    • , Fabienne Garzia
    • , Feroze Golamaully
    • , Gislain Septier
    •  & Jean-François Deleuze
  10. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Joshua C Bis
    • , Jennifer A Brody
    •  & Bruce M Psaty
  11. Dr. John T. Macdonald Foundation, Department of Human Genetics, University of Miami, Miami, Florida, USA.

    • Eden R Martin
    • , Gary W Beecham
    • , John R Gilbert
    •  & Margaret A Pericak-Vance
  12. Institute of Human Genetics, University of Bonn, Bonn, Germany.

    • Stefanie Heilmann-Heimbach
    • , Per Hoffmann
    • , Markus M Nöthen
    • , Stefan Herms
    • , Andreas J Forstner
    •  & Alfredo Ramirez
  13. Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.

    • Stefanie Heilmann-Heimbach
    • , Per Hoffmann
    • , Markus M Nöthen
    • , Stefan Herms
    •  & Andreas J Forstner
  14. Boston University School of Medicine, Boston, Massachusetts, USA.

    • Vincent Chouraki
    • , Seung-Hoan Choi
    • , Claudia L Satizabal
    • , Daniel Levy
    • , Jayanadra J Himali
    • , Lindsay A Farrer
    •  & Sudha Seshadri
  15. Framingham Heart Study, Framingham, Massachusetts, USA.

    • Vincent Chouraki
    • , Claudia L Satizabal
    • , L Adrienne Cupples
    • , Daniel Levy
    • , Alexa S Beiser
    • , Christopher J O'Donnell
    • , Anita L DeStefano
    •  & Sudha Seshadri
  16. Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

    • Amanda B Kuzma
    • , Otto Valladares
    • , Liming Qu
    • , Yi Zhao
    • , John Malamon
    • , Beth Dombroski
    • , Laura B Cantwell
    • , Li-San Wang
    •  & Gerard D Schellenberg
  17. Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.

    • Kristel Sleegers
    •  & Christine Van Broeckhoven
  18. Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.

    • Kristel Sleegers
    • , Sebastien Engelborghs
    • , Peter P De Deyn
    •  & Christine Van Broeckhoven
  19. Research Center and Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain.

    • Agustin Ruiz
    • , Sonia Moreno-Grau
    • , Isabel Henández
    • , Lluis Tarraga
    • , Oscar Sotolongo-Grau
    •  & Merce Boada
  20. Immunology Biomarkers Group, Genentech, South San Francisco, California, USA.

    • Robert R Graham
    •  & Timothy W Behrens
  21. Division of Medical Genetics, University Hospital and Department of Biomedicine, University of Basel, Basel, Switzerland.

    • Per Hoffmann
    •  & Stefan Herms
  22. School of Public Health, Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA.

    • Megan L Grove
    •  & Eric Boerwinkle
  23. Taub Institute on Alzheimer's Disease and the Aging Brain, Department of Neurology, Columbia University, New York, New York, USA.

    • Badri N Vardarajan
    • , Sandra Barral
    • , Lawrence S Honig
    • , Jennifer Williamson
    •  & Richard Mayeux
  24. Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA.

    • Badri N Vardarajan
    • , Sandra Barral
    • , Christiane Reitz
    •  & Richard Mayeux
  25. Department of Neurology, Columbia University, New York, New York, USA.

    • Badri N Vardarajan
    • , Sandra Barral
    • , Christiane Reitz
    •  & Richard Mayeux
  26. Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.

    • Mikko Hiltunen
  27. Department of Neurology, Kuopio University Hospital, Kuopio, Finland.

    • Mikko Hiltunen
    • , Hilkka Soininen
    • , Seppo Helisalmi
    • , Anne Maria Koivisto
    •  & Annakaisa Haapasalo
  28. Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • Charles C White
  29. UMR 894, Center for Psychiatry and Neuroscience, INSERM, Université Paris Descartes, Paris, France.

    • Jacques Epelbaum
  30. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

    • Wolfgang Maier
    •  & Frank Jessen
  31. Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.

    • Wolfgang Maier
    • , Frank Jessen
    • , Reinhard Heun
    •  & Alfredo Ramirez
  32. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.

    • Seung-Hoan Choi
    • , Josée Dupuis
    • , L Adrienne Cupples
    • , Alexa S Beiser
    • , Yuning Chen
    • , Qiong Yang
    • , Shuo Li
    •  & Anita L DeStefano
  33. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    • Albert V Smith
    •  & Vilmundur Gudnason
  34. Institute for Systems Biology, Seattle, Washington, USA.

    • Cory C Funk
    • , Hongdong Li
    •  & Nathan D Price
  35. School of Biotechnology, Dublin City University, Dublin, Ireland.

    • Denise Harold
  36. Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.

    • Alessio Squassina
  37. Neurology Service and CIBERNED, 'Marqués de Valdecilla' University Hospital (University of Cantabria and IFIMAV), Santander, Spain.

    • Pascual Sánchez-Juan
    •  & Onofre Combarros
  38. Department of Immunology, Hospital Universitario Doctor Negrín, Las Palmas de Gran Canaria, Spain.

    • Florentino Sanchez Garcia
    • , Maria Candida Deniz Naranjo
    • , Carmen Muñoz Fernadez
    •  & Yoland Aladro Benito
  39. Brown Foundation Institute of Molecular Medicine, University of Texas Health Sciences Center at Houston, Houston, Texas, USA.

    • Myriam Fornage
    •  & Xueqiu Jian
  40. Departments of Medicine, Geriatrics, Gerontology and Neurology, University of Mississippi Medical Center, Jackson, Mississippi, USA.

    • Thomas H Mosley
  41. Centre Hospitalier du Rouvray, Sotteville les Rouen, France.

    • David Wallon
    •  & Dominique Campion
  42. INSERM U1079, Rouen University, IRIB, Normandy University, Rouen, France.

    • David Wallon
    • , Didier Hannequin
    •  & Dominique Campion
  43. Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

    • Michelle K Lupton
    • , Petra Proitsi
    • , Yogen Patel
    • , Joseph T Hughes
    •  & John Powell
  44. Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.

    • Michelle K Lupton
  45. Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.

    • Laura Fratiglioni
    •  & Caroline Graff
  46. Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden.

    • Laura Fratiglioni
    •  & Lina Keller
  47. Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham, UK.

    • Christopher Medway
    • , Kristelle Brown
    • , Jenny Lord
    • , James Turton
    •  & Kevin Morgan
  48. Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Shubhabrata Mukherjee
    • , Paul K Crane
    • , Wayne C McCormick
    • , Chang-En Yu
    •  & Eric B Larson
  49. Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.

    • Honghuang Lin
  50. Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy.

    • Francesco Panza
  51. Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, UK.

    • Bernadette McGuinness
    • , Stephen Todd
    • , David Craig
    • , Janet Johnston
    •  & Peter Passmore
  52. Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.

    • Jeremy D Burgess
    • , Mariet Allen
    • , Xue Wang
    • , Minerva M Carrasquillo
    • , Neill R Graff-Radford
    • , Nilufer Ertekin-Taner
    • , Steven G Younkin
    •  & Dennis W Dickson
  53. Geriatric Medicine–Memory Unit and Rare Disease Centre, University of Bari Aldo Moro, Bari, Italy.

    • Vincenzo Solfrizzi
  54. Geriatric Unit and Gerontology–Geriatrics Research Laboratory, Department of Medical Sciences, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

    • Davide Seripa
    • , Maria Urbano
    •  & Alberto Pilotto
  55. Section of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy.

    • Pau Pastor
    • , Patrizia Mecocci
    • , Virginia Boccardi
    •  & Roberta Cecchetti
  56. Department of Neurology, Rouen University Hospital, Rouen, France.

    • Didier Hannequin
  57. Department of Neurology, University Hospital La Paz, Universidad Autónoma de Madrid, Madrid, Spain.

    • Ana Frank-García
  58. Instituto de Investigación Sanitaria Hospital la Paz (IdiPAZ), Madrid, Spain.

    • Ana Frank-García
    •  & María J Bullido
  59. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.

    • Ana Frank-García
    • , Mònica Díez Fairén
    • , Alberto Lleó
    • , Juan Fortea
    • , Rafael Blesa
    • , María J Bullido
    • , Jordi Clarimón
    • , Bruce M Psaty
    •  & Sara Ortega-Cubero
  60. National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.

    • Daniel Levy
  61. Center for Translational Research in Neurodegenerative Disease, Department of Neuroscience, University of Florida, Gainesville, Florida, USA.

    • Paramita Chakrabarty
    • , Carolina Ceballos Diaz
    •  & Todd E Golde
  62. Department of Neuroscience, University of Parma, Parma, Italy.

    • Paolo Caffarra
    •  & Letizia Concari
  63. Center for Cognitive Disorders AUSL, Parma, Italy.

    • Paolo Caffarra
    •  & Letizia Concari
  64. Department of Psychiatry, Martin Luther University Halle-Wittenberg, Halle, Germany.

    • Ina Giegling
    • , Annette M Hartmann
    •  & Dan Rujescu
  65. Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden.

    • Vilmantas Giedraitis
    • , Lars Lannfelt
    • , Lena Kilander
    • , RoseMarie Brundin
    •  & Martin Ingelsson
  66. AXA Research Fund and UPMC Chair, Paris, France.

    • Harald Hampel
  67. Sorbonne Universités, Université Pierre et Marie Curie, Paris, France.

    • Harald Hampel
  68. Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A) and Institut du Cerveau et de la Moelle Épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, Paris, France.

    • Harald Hampel
  69. Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Bethesda, Maryland, USA.

    • Melissa E Garcia
    •  & Lenore J Launer
  70. Centre Hospitalier Universitaire de Lille, Epidemiology and Public Health Department, Lille, France.

    • Florence Pasquier
    •  & Philippe Amouyel
  71. INSERM UMRS 1171, CNR-Maj, Lille, France.

    • Florence Pasquier
  72. Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, USA.

    • Robert C Barber
  73. Department of Primary Medical Care, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

    • Martin Scherer
  74. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

    • Perrie M Adams
  75. Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany.

    • Markus Leber
    • , Frank Jessen
    •  & Alfredo Ramirez
  76. Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.

    • Marilyn S Albert
  77. Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, Leipzig, Germany.

    • Steffi Riedel-Heller
  78. Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.

    • Valur Emilsson
  79. National Alzheimer's Coordinating Center, University of Washington, Seattle, Washington, USA.

    • Duane Beekly
  80. Schools of Life Sciences and Medicine, University of Nottingham, Nottingham, UK.

    • Anne Braae
    • , Imelda S Barber
    •  & Keeley Brookes
  81. Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz, Austria.

    • Reinhold Schmidt
  82. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Deborah Blacker
  83. Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.

    • Deborah Blacker
  84. Department of Neurology, Catholic University of Rome, Rome, Italy.

    • Carlo Masullo
  85. Institute of Molecular Biology and Biochemistry, Medical University Graz, Graz, Austria.

    • Helena Schmidt
  86. Alzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, Houston, Texas, USA.

    • Rachelle S Doody
  87. Experimental Neuropsychiatry Laboratory, IRCCS Santa Lucia Foundation, Department of Clinical and Behavioural Neurology, Rome, Italy.

    • Gianfranco Spalletta
    • , Paola Bossù
    • , Eleonora Sacchinelli
    • , Carlo Caltagirone
    • , Maria Donata Orfei
    •  & Antonio Ciaramella
  88. Department of Neurology, University of Washington, Seattle, Washington, USA.

    • W T Longstreth Jr
    •  & Thomas D Bird
  89. Department of Epidemiology, University of Washington, Seattle, Washington, USA.

    • W T Longstreth Jr
    • , Annette L Fitzpatrick
    • , Walter A Kukull
    •  & Bruce M Psaty
  90. Office of Strategy and Measurement, University of North Texas Health Science Center, Fort Worth, Texas, USA.

    • Thomas J Fairchild
  91. Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Oscar L Lopez
  92. Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Oscar L Lopez
  93. C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.

    • Matthew P Frosch
  94. Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, Indiana, USA.

    • Bernardino Ghetti
    • , Jill R Murrell
    •  & Salvatore Spina
  95. Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

    • Ryan M Huebinger
  96. Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • M Ilyas Kamboh
  97. Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • M Ilyas Kamboh
  98. Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.

    • John Morris
    •  & Carlos Cruchaga
  99. Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St. Louis, Missouri, USA.

    • John Morris
    •  & Carlos Cruchaga
  100. Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA.

    • Mindy J Katz
    •  & Richard B Lipton
  101. Department of Mathematics and Statistics, Utah State University, Logan, Utah, USA.

    • Chris Corcoran
    • , JoAnn Tschanz
    • , Maria Norton
    •  & Ron Munger
  102. Fundació per la Recerca Biomèdica i Social Mútua Terrassa, Terrassa, Barcelona, Spain.

    • Miquel Aguilar
    •  & Mònica Díez Fairén
  103. Memory Unit, Department of Neurology, Hospital Universitario Mútua Terrassa, Terrassa, Barcelona, Spain.

    • Miquel Aguilar
  104. Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

    • Angela Hodges
  105. INSERM U558, University of Toulouse, Toulouse, France.

    • Bruno Vellas
  106. Elderly and Psychiatric Disorders Department, Medical University of Lodz, Lodz, Poland.

    • Iwona Kloszewska
  107. Department of Health Sciences, Psychiatry for the Elderly, University of Leicester, Leicester, UK.

    • Makrina Daniilidou
  108. Department of Neurodegenerative Disease, MRC Prion Unit, UCL Institute of Neurology, London, UK.

    • James Uphill
    • , John Collinge
    • , Simon Mead
    •  & Andre G Uitterlinden
  109. Department of Pathophysiology and Transplantation, University of Milan, Fondazione Ca' Granda, IRCCS Ospedale Policlinico, Milan, Italy.

    • Chiara Fenoglio
    • , Maria Serpente
    • , Marina Arcaro
    • , Daniela Galimberti
    • , Elio Scarpini
    •  & Andre G Uitterlinden
  110. Department of Psychiatry and Psychotherapy, University Hospital, Saarland, Germany.

    • Sabrina Pichler
    • , Manuel Mayhaus
    • , Wei Gu
    •  & Matthias Riemenschneider
  111. Memory Unit, Neurology Department and Sant Pau Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.

    • Alberto Lleó
    • , Juan Fortea
    • , Rafael Blesa
    •  & Jordi Clarimón
  112. Regional Neurogenetic Centre (CRN), ASP Catanzaro, Lamezia Terme, Italy.

    • Chiara Cupidi
    • , Raffaele Giovanni Maletta
    • , Maura Gallo
    •  & Amalia Cecilia Bruni
  113. Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington, USA.

    • David Carrell
    • , Ge Li
    • , Elaine Peskind
    • , Murray Raskind
    •  & Debby W Tsuang
  114. NEUROFARBA (Department of Neuroscience, Psychology, Drug Research and Child Health), University of Florence, Florence, Italy.

    • Sandro Sorbi
    •  & Benedetta Nacmias
  115. IRCCS 'Don Carlo Gnocchi', Florence, Italy.

    • Sandro Sorbi
    •  & Benedetta Nacmias
  116. Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.

    • Susanne Moebus
  117. Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany.

    • Johannes Kornhuber
  118. Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Associazione Oasi Maria Santissima Srl, Troina, Italy.

    • Paolo Bosco
  119. Mercers Institute for Research on Aging, St. James Hospital and Trinity College, Dublin, Ireland.

    • Michael Gill
    • , Brian Lawlor
    •  & Aoibhinn Lynch
  120. Department of Molecular Neuroscience, UCL, Institute of Neurology, London, UK.

    • Nick C Fox
    • , John Hardy
    • , Jose Bras
    •  & Rita Guerreiro
  121. Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.

    • Roger L Albin
    •  & Henry L Paulson
  122. Geriatric Research, Education and Clinical Center (GRECC), VA Ann Arbor Healthcare System (VAAAHS), Ann Arbor, Michigan, USA.

    • Roger L Albin
  123. Michigan Alzheimer Disease Center, Ann Arbor, Michigan, USA.

    • Roger L Albin
    •  & Henry L Paulson
  124. Indiana Alzheimer's Disease Center, Indiana University School of Medicine, Indianapolis, Indiana, USA.

    • Liana G Apostolova
  125. Department of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana, USA.

    • Liana G Apostolova
    • , Kelley M Faber
    • , Tatiana M Foroud
    • , Jill R Murrell
    •  & Andrew J Saykin
  126. Department of Neurology, Indiana University, Indianapolis, Indiana, USA.

    • Liana G Apostolova
    •  & Martin R Farlow
  127. Department of Radiology and Imaging Sciences, Indiana University, Indianapolis, Indiana, USA.

    • Liana G Apostolova
    •  & Andrew J Saykin
  128. Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

    • Steven E Arnold
  129. Geriatric Research, Education and Clinical Center (GRECC), University of Wisconsin, Madison, Wisconsin, USA.

    • Sanjay Asthana
    •  & Craig S Atwood
  130. Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA.

    • Sanjay Asthana
    • , Craig S Atwood
    • , Cynthia M Carlsson
    •  & Mark A Sager
  131. Wisconsin Alzheimer's Disease Research Center, Madison, Wisconsin, USA.

    • Sanjay Asthana
    • , Craig S Atwood
    •  & Cynthia M Carlsson
  132. Department of Medicine (Genetics Program), Boston University, Boston, Massachusetts, USA.

    • Clinton T Baldwin
    • , Gyungah Jun
    •  & Lindsay A Farrer
  133. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.

    • Lisa L Barnes
    • , Julie A Schneider
    • , Lei Yu
    •  & David A Bennett
  134. Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois, USA.

    • Lisa L Barnes
  135. Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.

    • Lisa L Barnes
    • , Julie A Schneider
    • , Lei Yu
    •  & David A Bennett
  136. Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Phoenix, Arizona, USA.

    • Thomas G Beach
  137. Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

    • James T Becker
  138. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

    • Eileen H Bigio
  139. Cognitive Neurology and Alzheimer's Disease Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

    • Eileen H Bigio
    • , Marsel Mesulam
    •  & Sandra Weintraub
  140. VA Puget Sound Health Care System/GRECC, Seattle, Washington, USA.

    • Thomas D Bird
    • , Ge Li
    • , Debby W Tsuang
    •  & Clive Holmes
  141. Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.

    • Bradley F Boeve
    •  & Ronald C Petersen
  142. Swedish Medical Center, Seattle, Washington, USA.

    • James D Bowen
  143. Department of Neurology, University of California, San Francisco, San Francisco, California, USA.

    • Adam Boxer
    • , Anna Karydas
    • , Bruce L Miller
    • , Howard J Rosen
    •  & William W Seeley
  144. Department of Medicine, Duke University, Durham, North Carolina, USA.

    • James R Burke
    •  & Kathleen A Welsh-Bohmer
  145. University of Kansas Alzheimer's Disease Center, University of Kansas Medical Center, Kansas City, Kansas, USA.

    • Jeffrey M Burns
    •  & Russell H Swerdlow
  146. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA.

    • Joseph D Buxbaum
  147. Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USA.

    • Joseph D Buxbaum
    •  & Alison M Goate
  148. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA.

    • Joseph D Buxbaum
    •  & Mary Sano
  149. Department of Pathology and Immunology, Washington University, St. Louis, Missouri, USA.

    • Nigel J Cairns
    •  & John C Morris
  150. USF Health Byrd Alzheimer's Institute, University of South Florida, Tampa, Florida, USA.

    • Chuanhai Cao
    • , Ashok Raj
    •  & Amanda G Smith
  151. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

    • Chris S Carlson
    •  & Andrew N McDavid
  152. Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, Florida, USA.

    • Regina M Carney
    • , Elizabeth A Crocco
    •  & Amanda J Myers
  153. Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.

    • Steven L Carroll
  154. Department of Neurology, University of Southern California, Los Angeles, California, USA.

    • Helena C Chui
    •  & Lon S Schneider
  155. Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, USA.

    • David G Clark
  156. Department of Neurology, Ralph H. Johnson VA Medical Center, Charleston, South Carolina, USA.

    • David G Clark
  157. Department of Neurology, University of California, Irvine, Irvine, California, USA.

    • David H Cribbs
    •  & Aimee Pierce
  158. Department of Neurology, University of California, Davis, Sacramento, California, USA.

    • Charles DeCarli
    •  & John M Olichney
  159. Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California, USA.

    • Malcolm Dick
    •  & Wayne W Poon
  160. Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, Florida, USA.

    • Ranjan Duara
  161. Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois, USA.

    • Denis A Evans
  162. Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

    • Kenneth B Fallon
  163. Sanders-Brown Center on Aging, Department of Biostatistics, University of Kentucky, Lexington, Kentucky, USA.

    • David W Fardo
  164. Department of Psychiatry, New York University, New York, New York, USA.

    • Steven Ferris
    •  & Barry Reisberg
  165. Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.

    • Douglas R Galasko
    •  & Eliezer Masliah
  166. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.

    • Marla Gearing
  167. Emory Alzheimer's Disease Center, Emory University, Atlanta, Georgia, USA.

    • Marla Gearing
  168. Neurogenetics Program, University of California, Los Angeles, Los Angeles, California, USA.

    • Daniel H Geschwind
  169. Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.

    • Neill R Graff-Radford
    • , Nilufer Ertekin-Taner
    •  & Steven G Younkin
  170. Division of Genetics, Department of Medicine and Partners Center for Personalized Genetic Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • Robert C Green
  171. Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA.

    • John H Growdon
    • , Bradley T Hyman
    •  & Rudolph E Tanzi
  172. Department of Pathology (Neuropathology), University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

    • Ronald L Hamilton
  173. Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

    • Lindy E Harrell
    • , Daniel C Marson
    •  & Erik D Roberson
  174. Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona, USA.

    • Matthew J Huentelman
    •  & Eric M Reiman
  175. Department of Pathology, Duke University, Durham, North Carolina, USA.

    • Christine M Hulette
  176. Department of Genome Sciences, University of Washington, Seattle, Washington, USA.

    • Gail P Jarvik
  177. Department of Medicine (Medical Genetics), University of Washington, Seattle, Washington, USA.

    • Gail P Jarvik
  178. Sanders-Brown Center on Aging, College of Public Health, Department of Epidemiology, University of Kentucky, Lexington, Kentucky, USA.

    • Erin Abner
  179. Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, California, USA.

    • Lee-Way Jin
    •  & Joshua W Miller
  180. Department of Biostatistics, Boston University, Boston, Massachusetts, USA.

    • Gyungah Jun
    • , Kathryn L Lunetta
    •  & Lindsay A Farrer
  181. Department of Ophthalmology, Boston University, Boston, Massachusetts, USA.

    • Gyungah Jun
    •  & Lindsay A Farrer
  182. Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA.

    • Jeffrey A Kaye
    •  & Joseph F Quinn
  183. Department of Neurology, Portland Veterans Affairs Medical Center, Portland, Oregon, USA.

    • Jeffrey A Kaye
    •  & Joseph F Quinn
  184. Department of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, California, USA.

    • Ronald Kim
  185. Department of Neurology, Boston University, Boston, Massachusetts, USA.

    • Neil W Kowall
    • , Ann C McKee
    • , Robert A Stern
    •  & Lindsay A Farrer
  186. Department of Pathology, Boston University, Boston, Massachusetts, USA.

    • Neil W Kowall
    •  & Ann C McKee
  187. Department of Neuropsychology, University of California, San Francisco, San Francisco, California, USA.

    • Joel H Kramer
  188. Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California, USA.

    • Frank M LaFerla
  189. Department of Neurology, Emory University, Atlanta, Georgia, USA.

    • James J Lah
    • , Allan I Levey
    •  & Thomas S Wingo
  190. Cleveland Clinic Lou Ruvo Center for Brain Health, Cleveland Clinic, Cleveland, Ohio, USA.

    • James B Leverenz
  191. Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.

    • Andrew P Lieberman
  192. Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland, USA.

    • Constantine G Lyketsos
  193. Department of Medicine–Pulmonary, New York University, New York, New York, USA.

    • Frank Martiniuk
  194. Department of Neurology, University of Miami, Miami, Florida, USA.

    • Deborah C Mash
  195. Department of Pathology, University of California, San Diego, La Jolla, California, USA.

    • Eliezer Masliah
  196. School of Nursing Northwest Research Group on Aging, University of Washington, Seattle, Washington, USA.

    • Susan M McCurry
  197. Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

    • Marsel Mesulam
  198. Department of Pathology, University of Southern California, Los Angeles, California, USA.

    • Carol A Miller
  199. Department of Neurology, Washington University, St. Louis, Missouri, USA.

    • John C Morris
  200. Internal Medicine, Division of Geriatrics, University of North Texas Health Science Center, Fort Worth, Texas, USA.

    • Sid O'Bryant
  201. Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.

    • Vernon S Pankratz
  202. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.

    • Joseph E Parisi
  203. Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA.

    • Huntington Potter
  204. Alzheimer's Disease Center, New York University, New York, New York, USA.

    • Barry Reisberg
  205. Department of Epidemiology, Columbia University, New York, New York, USA.

    • Christiane Reitz
  206. Department of Neurology, University of California, Los Angeles, Los Angeles, California, USA.

    • John M Ringman
    •  & Harry V Vinters
  207. Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada.

    • Ekaterina Rogaeva
    •  & Peter St George-Hyslop
  208. Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

    • Roger N Rosenberg
  209. Department of Pathology (Neuropathology), Rush University Medical Center, Chicago, Illinois, USA.

    • Julie A Schneider
  210. Department of Psychiatry, University of Southern California, Los Angeles, California, USA.

    • Lon S Schneider
  211. Department of Pathology, University of Washington, Seattle, Washington, USA.

    • Joshua A Sonnen
    • , C Dirk Keene
    •  & Thomas J Montine
  212. Translational Medicine, Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA.

    • Tricia A Thornton-Wells
  213. Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

    • John Q Trojanowski
    •  & Vivianna M Van Deerlin
  214. Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.

    • Juan C Troncoso
  215. Sanders-Brown Center on Aging, Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, USA.

    • Linda J Van Eldik
  216. Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California, USA.

    • Harry V Vinters
  217. Taub Institute on Alzheimer's Disease and the Aging Brain, Department of Pathology, Columbia University, New York, New York, USA.

    • Jean Paul Vonsattel
  218. Department of Psychiatry, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

    • Sandra Weintraub
  219. Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, USA.

    • Kathleen A Welsh-Bohmer
  220. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

    • Kirk C Wilhelmsen
  221. Department of Pathology, Oregon Health & Science University, Portland, Oregon, USA.

    • Randall L Woltjer
  222. Evelyn F. McKnight Brain Institute, Department of Neurology, Miller School of Medicine, University of Miami, Miami, Florida, USA.

    • Clinton B Wright
  223. Department of Neurology and Memory Clinic, Hospital Network Antwerp, Antwerp, Belgium.

    • Sebastien Engelborghs
    • , Rik Vandenberghe
    •  & Peter P De Deyn
  224. Laboratory for Cognitive Neurology, Department of Neurology, University of Leuven, Leuven, Belgium.

    • Rik Vandenberghe
  225. Department of Geriatric Medicine, Genetics Unit, Karolinska University Hospital Huddinge, Stockholm, Sweden.

    • Hakan Thonberg
    • , Charlotte Forsell
    • , Lena Lilius
    •  & Anne Kinhult-Stählbom
  226. Department of Neurobiology, Care Sciences and Society, KIADRC, Karolinska Institutet, Stockholm, Sweden.

    • Hakan Thonberg
    • , Charlotte Forsell
    • , Lena Lilius
    • , Anne Kinhult-Stählbom
    •  & Caroline Graff
  227. Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland.

    • Seppo Helisalmi
    • , Anne Maria Koivisto
    •  & Annakaisa Haapasalo
  228. CHU Lille, Memory Center of Lille (Centre Mémoire de Ressources et de Recherche), Lille, France.

    • Vincent Dermecourt
  229. University Paris Descartes, EA 4468, AP–HP, Hôpital Broca, Geriatrics Department, Paris, France.

    • Nathalie Fievet
    •  & Olivier Hanon
  230. University of Bordeaux, Neuroepidemiology, Bordeaux, France.

    • Carole Dufouil
  231. INSERM, Neuroepidemiology, UMR 897, Bordeaux, France.

    • Carole Dufouil
  232. INSERM U1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06, UMRS 1127, Institut du Cerveau et de la Moelle Épinière, Paris, France.

    • Alexis Brice
    •  & Christophe Tzourio
  233. AP–HP, Department of Genetics, Pitié-Salpêtrière Hospital, Paris, France.

    • Alexis Brice
  234. INSERM U1061, La Colombière Hospital, Montpellier, France.

    • Karen Ritchie
  235. Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A), Département de Neurologie, Hôpital de la Pitié-Salpêtrière, AP–HP, Paris, France.

    • Bruno Dubois
    •  & Claudine Berr
  236. Institut des Neurosciences Translationnelles de Paris (IHU-A-ICM), Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France.

    • Bruno Dubois
  237. INSERM, CNRS, UMRS 975, Institut du Cerveau et de la Moelle Épinière (ICM), Paris, France.

    • Bruno Dubois
  238. Sorbonne Universités, Université Pierre et Marie Curie, Hôpital de la Pitié-Salpêtrière, AP–HP, Paris, France.

    • Bruno Dubois
  239. Department of Family Medicine, University of Washington, Seattle, Washington, USA.

    • Annette L Fitzpatrick
  240. Centre for Public Health, University of Iceland, Reykjavik, Iceland.

    • Thor Aspelund
  241. Group Health Research Institute, Group Health, Seattle, Washington, USA.

    • Eric B Larson
  242. Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA.

    • Jerome I Rotter
  243. Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.

    • María J Bullido
  244. Molecular Genetics Laboratory-Hospital, University of Central Asturias, Oviedo, Spain.

    • Eliecer Coto
    •  & Victoria Alvarez
  245. Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.

    • Eric Boerwinkle
  246. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.

    • Fernando Rivadeneira
  247. Netherlands Consortium on Health Aging and National Genomics Initiative, Leiden, the Netherlands.

    • Fernando Rivadeneira
  248. Arizona Alzheimer's Consortium, Phoenix, Arizona, USA.

    • Eric M Reiman
  249. Banner Alzheimer's Institute, Phoenix, Arizona, USA.

    • Eric M Reiman
  250. Department of Psychiatry, University of Arizona, Phoenix, Arizona, USA.

    • Eric M Reiman
  251. Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

    • Joan S Reisch
  252. Departments of Psychiatry, Medicine, and Family and Community Medicine and South Texas Veterans Health Administration Geriatric Research Education and Clinical Center (GRECC), University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

    • Donald R Royall
  253. Institute for Stroke and Dementia Research, Klinikum der Universität München, Munich, Germany.

    • Martin Dichgans
  254. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.

    • Martin Dichgans
  255. Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.

    • Peter St George-Hyslop
    •  & David C Rubinsztein
  256. Department of Experimental and Clinical Medicine, Neurological Institute, University of Pisa, Pisa, Italy.

    • Michelangelo Mancuso
    •  & Ubaldo Bonuccelli
  257. PharmaTherapeutics Clinical Research, Pfizer Worldwide Research and Development, Cambridge, Massachusetts, USA.

    • Ashley R Winslow
  258. Institute of Neurology, Catholic University of Sacred Hearth, Rome, Italy.

    • Antonio Daniele
  259. Departments of Neurology, Pharmacology, and Neuroscience, Texas Tech University Health Science Center, Lubbock, Texas, USA.

    • Chuang-Kuo Wu
  260. Department of Psychiatry, Charité University Medicine, Berlin, Germany.

    • Oliver Peters
  261. Institute of Public Health, University of Cambridge, Cambridge, UK.

    • Carol Brayne
  262. Department of Medical Sciences, Institute of Biomedicine (iBiMED), University of Aveiro, Aveiro, Portugal.

    • Jose Bras
    •  & Rita Guerreiro
  263. Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

    • Ammar Al-Chalabi
    •  & Christopher E Shaw
  264. Institute of Brain, Behaviour and Mental Health, Clinical and Cognitive Neuroscience Research Group, University of Manchester, Manchester, UK.

    • David Mann
  265. 3rd Department of Neurology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

    • Magda Tsolaki
  266. Division of Clinical Neurosciences, School of Medicine, University of Southampton, Southampton, UK.

    • Rebecca Sussams
  267. Department of Psychiatry, University of Oxford, Oxford, UK.

    • Simon Lovestone
  268. Florida Alzheimer's Disease Research Center, Gainesville, Florida, USA.

    • Todd E Golde
  269. Center for Translational and Systems Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, New York, USA.

    • Philip L De Jager
  270. Department of Health Services, University of Washington, Seattle, Washington, USA.

    • Bruce M Psaty
  271. Memory Research and Resources Center, CMRR of Montpellier, Department of Neurology, Hospital Gui de Chauliac, Montpellier, France.

    • Claudine Berr
  272. Department of Neurology, Montpellier University, Montpellier, France.

    • Claudine Berr
  273. Memory Research and Resources Center, CMRR de Bordeaux, Bordeaux, France.

    • Jean-François Dartigues
  274. Neurogenetics Laboratory, Division of Neurosciences, Centre for Applied Medical Research, University of Navarra School of Medicine, Pamplona, Spain.

    • Sara Ortega-Cubero
  275. Department of Neurology, Complejo Asistencial Universitario de Palencia, Palencia, Spain.

    • Sara Ortega-Cubero
  276. Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

    • Hakon Hakonarson
  277. Departments of Biology and Neuroscience, Brigham Young University, Provo, Utah, USA.

    • John Keoni Kauwe
  278. Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

    • M Arfan Ikram
  279. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.

    • Jonathan L Haines
  280. University of Bordeaux, Neuroepidemiology, UMR 897, Bordeaux, France.

    • Christophe Tzourio

Consortia

  1. ARUK Consortium

  2. GERAD/PERADES, CHARGE, ADGC, EADI

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