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A Nonsynonymous Mutation in PLCG2 Reduces the Risk of Alzheimer's Disease, Dementia with Lewy-Bodies and Frontotemporal Dementia, and Increases the Likelihood of Longevity

37 Pages Posted: 1 Feb 2019

See all articles by Sven J. van der Lee

Sven J. van der Lee

VU University Amsterdam

Olivia J. Conway

Mayo Clinic - Florida

Iris Jansen

VU University Amsterdam - Department of Neurology

Minerva M. Carrasquillo

Mayo Clinic - Florida

Luca Kleineidam

University of Cologne - Division of Neurogenetics and Molecular Psychiatry

Erik van den Akker

Leiden University - Medical Center (LUMC)

Isabel Hernández

Universitat Internacional de Catalunya

Kristel R. Van Eijk

Utrecht University - Department of Neurology

Najada Stringa

VU University Amsterdam - Amsterdam Public Health Research Institute

Jason A. Chen

University of California, Los Angeles (UCLA)

Anna Zettergren

Göteborg University

Till F. M. Andlauer

Max Planck Institute of Psychiatry

Monica Diez-Fairen

Hospital Universitario Mutua de Terrassa

Javier Simon-Sanchez

German Center for Neurodegenerative Diseases (DZNE)

Alberto Lleó

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Henrik Zetterberg

Göteborg University - Institute of Neuroscience and Physiology

Marianne Nygaard

University of Southern Denmark

Cornelis Blauwendraat

Government of the United States of America - National Institute of Neurological Disorders and Stroke (NINDS)

Jeanne E. Savage

VU University Amsterdam

Jonas Mengel-From

University of Southern Denmark

Sonia Moreno-Grau

Universitat Internacional de Catalunya

Michael Wagner

Bonn University

Juan Fortea

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Michael J. Keogh

University of Newcastle

Kaj Blennow

Göteborg University - Institute of Neuroscience and Physiology; Göteborg University - Sahlgrenska University Hospital

Ingmar Skoog

Göteborg University

Manuel A. Friese

German Competence Network Multiple Sclerosis (KKNMS)

Olga Pletnikova

Johns Hopkins University - School of Medicine

Miren Zulaica

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Carmen Lage

affiliation not provided to SSRN

Itziar de Rojas

Carlos III Institute of Health

Steffi Riedel-Heller

University of Leipzig - Institute for Social Medicine, Occupational Health and Public Health

Ignacio Illán-Gala

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Wei Wei

University of Cambridge

Bernard Jeune

University of Southern Denmark

Adela Orellana

Universitat Internacional de Catalunya

Florian Then Bergh

German Competence Network Multiple Sclerosis (KKNMS)

Xue Wang

Mayo Clinic - Florida

Marc Hulsman

VU University Amsterdam - Department of Neurology

Nina Beker

VU University Amsterdam

Niccolo Tesí

VU University Amsterdam

Christopher Morris

University of Newcastle

Begoña Indakoetxea

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Lyduine E. Collij

VU University Medical Center

Martin Scherer

University Medical Center Hamburg-Eppendorf

Estrella Morenas-Rodríguez

Utrecht University - University Medical Center (Utrecht)

James W. Ironside

University of Edinburgh

Bart. N.M. van Berckel

VU University Medical Center

Daniel Alcolea

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Heinz Wiendl

German Competence Network Multiple Sclerosis (KKNMS)

Samantha L. Strickland

Mayo Clinic - Florida

Pau Pastor

Hospital Universitario Mutua de Terrassa

Eloy Rodríguez Rodríguez

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

DESGESCO Dementia Genetics Spanish Consortium

Alzheimer Disease European DNA Biobank

IFGC International FTD-Genomics Consortium

IPDGC The International Parkinson Disease Genomics Consortium

RiMod-FTD Rsk and Modifying factors in Fronto-Temporal Dementia

Netherlands Brain Bank (NBB)

Bradley F. Boeve

Mayo Clinic

Ronald C. Petersen

Mayo Clinic

Tanis J. Ferman

Mayo Clinic - Florida

Jay A. van Gerpen

Mayo Clinic - Florida

Marcel J. T. Reinders

Delft University of Technology

Ryan J. Uitti

Mayo Clinic - Florida

Lluis Tarraga

Universitat Internacional de Catalunya

Wolfgang Maier

University of Bonn - Department of Neurodegenerative Disease and Gerontopsychiatry

Oriol Dols-Icardo

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Amit Kawalia

University Hospital of Cologne

Maria Carolina Dalmasso

University Hospital of Cologne

Mercè Boada

Universitat Internacional de Catalunya

Uwe K. Zettl

German Competence Network Multiple Sclerosis (KKNMS)

Natasja M. van Schoor

University of Amsterdam - Amsterdam Public Health Research Institute

Marian Beekman

Leiden University - Section of Molecular Epidemiology

Mariet Allen

Mayo Clinic - Florida

Eliezer Masliah

National Institutes of Health (NIH)

Adolfo López de Munain

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Alexander Pantelyat

Johns Hopkins University - School of Medicine

Zbigniew K. Wszolek

Mayo Clinic - Florida

Owen A. Ross

Mayo Clinic - Florida

Dennis W. Dickson

Mayo Clinic - Florida

Neill R. Graff-Radford

Mayo Clinic - Florida

David Knopman

Mayo Clinic

Rosa Rademakers

Mayo Clinic - Florida - Department of Neuroscience

Afina W. Lemstra

VU University Amsterdam

Yolande A. L. Pijnenburg

VU University Amsterdam

Philip Scheltens

VU University Amsterdam - Department of Neurology

Thomas Gasser

University of Tuebingen

Patrick F. Chinnery

University Medical Center Hamburg-Eppendorf

Bernhard Hemmer

Technische Universität München (TUM)

Martijn A. Huisman

VU University Amsterdam - Amsterdam Public Health Research Institute

Juan Troncoso

Johns Hopkins University - Department of Pathology

Fermin Moreno

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Ellen A. Nohr

University of Southern Denmark - Institute of Clinical Research

Thorkild I. A. Sørensen

University of Copenhagen - Section of Metabolic Genetics

Peter Heutink

German Center for Neurodegenerative Diseases (DZNE)

Pascual Sánchez-Juan

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Danielle Posthuma

VU University Medical Center

Giovanni Coppola

University of California, Los Angeles (UCLA) - Department of Neurology

Jordi Clarimón

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Kaare Christensen

University of Southern Denmark

Nilüfer Ertekin-Taner

VU University Amsterdam

Sonja W. Scholz

National Institutes of Health - Neurodegenerative Diseases Research Unit

Alfredo Ramirez

University of Cologne - Division of Neurogenetics and Molecular Psychiatry; University of Bonn - Department of Neurodegenerative Disease and Gerontopsychiatry

Agustin Ruiz

Universitat Internacional de Catalunya

Eline Slagboom

Leiden University - Medical Center (LUMC)

Wiesje M. van der Flier

University of Bonn - Institute of Innate Immunity

Henne Holstege

VU University Amsterdam - Alzheimer Center Amsterdam; VU University Amsterdam - Department of Clinical Genetics

More...

Abstract

Background: PLCG2 plays an important role in immune system signaling, and is expressed in several immune cell types including microglia in the brain. In 2017, the genetic variant rs72824905 (p.Pro522Arg) in the PLCG2 gene (Phospholipase C Gamma 2) was associated with a reduced risk of Alzheimer's disease (AD). Here we investigated whether the rs72824905 variant had a similar protective effect on six other brain diseases. We further tested if rs72824905 increases the likelihood of longevity, since a reduced risk of neurodegenerative diseases might associate with general survival.    

Methods:  We investigated the effect of carrying rs72824905 on disease risk in a total of 53,627 patients with one of seven brain diseases. We studied AD (N = 4,985), frontotemporal dementia (FTD) (N = 2,437), dementia with Lewy-bodies (DLB) (N = 1,446), progressive supranuclear palsy (PSP) (N = 882), Parkinson's disease (PD) (N = 28,448) amyotrophic lateral sclerosis (ALS) (N = 10,953) and multiple sclerosis (MS) (N = 4,476) by comparing them with in total 149,290 controls using logistic regression models. Next, we studied the effect of carrying rs72824905 on longevity by comparing individuals who reached at least 90 years (N = 3,516) with individuals who died before age 90 years or were last screened before 90 years (N = 9,677). In addition, we studied the association of rs72824905 with survival after the age of 90 in a subset of long-lived individuals followed until death. Finally, we supported our findings by studying by-proxy phenotypes in the ~450.000 participants of the UK Biobank. We associated the rs72824905 genotypes of UK Biobank participants with parental history of dementia as proxy for dementia and as a proxy for longevity we studied parental age over 90 as well as parental age over 95 years of age. All individuals were of European ancestry.    

Results: The rs72824905-G allele associated with a reduced AD risk (Odds ratio (OR) = 0·57, p = 4·7×10-4), a reduced DLB risk (OR = 0·54, p = 4·5×10-2) and reduced FTD risk (OR = 0·61, p = 1·0×10 2). We did not find evidence for association of rs72824905 with the risks of PSP (OR = 1·46, p = 0·19), PD (OR = 1·18, p = 0·10), ALS (OR = 1·07, p = 0·26) or MS (OR = 0·99, p = 0·95). The rs72824905-G allele was associated with a 1·49 increased likelihood of reaching >90 years (p = 6.4×10-3): variant carriers lived longer after the age of 90 years, median 4.7 (inter quartile range = 1·9 - 7·4) years compared to non-carriers 3.3 (IQR = 1·4 - 5·8) (Hazard ratio = 0·75, p = 0·07). By-proxy analyses supported the associations of rs728824905 with dementia as well as longevity. Variant carriers had a lower likelihood of having a parent with dementia (OR = 0·88, p = 1·8×10 3) and had a significantly increased likelihood of having a parent aged >95 years (OR = 1·19, p = 2·1×10-2).

Conclusions: Our results show that rs72824905 in PLCG2 protects from AD, DLB and FTD and increases the likelihood of longevity. Together, our findings highlight a central role for PLCG2 related immune signaling in the brain, which should be the subject of future studies as a drug target for multiple brain diseases.   

Funding Statement: The authors present a short description of 16 cohorts, often including multiple sites or studies, that contributed to this manuscript and their funding sources in Supplementary Table 1: Amsterdam dementia Cohort (ADC), 100-Plus study, German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe), Brain compendium, Clinical AD, Sweden, Danish data, Fundació ACE (FACE), Genetics of Healthy Ageing Study (GEHA – NL), Gothenburg Birth Cohort (GBC) Studies, International FTD-Genomics Consortium (IFGC), Kompetenznetz Multiple Sklerose (KKNMS), Longitudinal Aging Study Amsterdam (LASA), Leiden Longevity Study, Maria Carolina Dalmasso, Mayo Clinic AD, DLB, PD, PSP, NDRU cohort, Oviedo, Pascual Sánchez-Juan, Project MinE, Risk and modifying factors in Fronto Temporal Dementia (RiMoD-FTD): follows The SPIN cohort, San Sebastian, UK Biobank analysis, IPDGC (The International Parkinson Disease Genomics Consortium).

Declaration of Interests: The authors declare no competing interest related to this work.

Ethics Approval Statement: Studies were approved by corresponding ethics committees and informed consent was obtained for all participants.

Keywords: Alzheimer's Disease, frontotemporal dementia, dementia with Lewy-bodies, progressive suprauclear palsy, Parkinson's Disease, amyotrophic lateral sclerosis, multiple sclerosis, neurodegenerative disease, longevity, PLCG2, Phospholipase C Gamma 2

Suggested Citation

van der Lee, Sven J. and Conway, Olivia J. and Jansen, Iris and Carrasquillo, Minerva M. and Kleineidam, Luca and Akker, Erik van den and Hernández, Isabel and Van Eijk, Kristel R. and Stringa, Najada and Chen, Jason A. and Zettergren, Anna and Andlauer, Till F. M. and Diez-Fairen, Monica and Simon-Sanchez, Javier and Lleó, Alberto and Zetterberg, Henrik and Nygaard, Marianne and Blauwendraat, Cornelis and Savage, Jeanne E. and Mengel-From, Jonas and Moreno-Grau, Sonia and Wagner, Michael and Fortea, Juan and Keogh, Michael J. and Blennow, Kaj and Skoog, Ingmar and Friese, Manuel A. and Pletnikova, Olga and Zulaica, Miren and Lage, Carmen and de Rojas, Itziar and Riedel-Heller, Steffi and Illán-Gala, Ignacio and Wei, Wei and Jeune, Bernard and Orellana, Adela and Bergh, Florian Then and Wang, Xue and Hulsman, Marc and Beker, Nina and Tesí, Niccolo and Morris, Christopher and Indakoetxea, Begoña and Collij, Lyduine E. and Scherer, Martin and Morenas-Rodríguez, Estrella and Ironside, James W. and Berckel, Bart. N.M. van and Alcolea, Daniel and Wiendl, Heinz and Strickland, Samantha L. and Pastor, Pau and Rodríguez, Eloy Rodríguez and Consortium, DESGESCO Dementia Genetics Spanish and Biobank, Alzheimer Disease European DNA and Consortium, IFGC International FTD-Genomics and Consortium, IPDGC The International Parkinson Disease Genomics and Dementia, RiMod-FTD Rsk and Modifying factors in Fronto-Temporal and Bank (NBB), Netherlands Brain and Boeve, Bradley F. and Petersen, Ronald C. and Ferman, Tanis J. and Gerpen, Jay A. van and Reinders, Marcel J. T. and Uitti, Ryan J. and Tarraga, Lluis and Maier, Wolfgang and Dols-Icardo, Oriol and Kawalia, Amit and Dalmasso, Maria Carolina and Boada, Mercè and Zettl, Uwe K. and van Schoor, Natasja M. and Beekman, Marian and Allen, Mariet and Masliah, Eliezer and Munain, Adolfo López de and Pantelyat, Alexander and Wszolek, Zbigniew K. and Ross, Owen A. and Dickson, Dennis W. and Graff-Radford, Neill R. and Knopman, David and Rademakers, Rosa and Lemstra, Afina W. and Pijnenburg, Yolande A. L. and Scheltens, Philip and Gasser, Thomas and Chinnery, Patrick F. and Hemmer, Bernhard and Huisman, Martijn A. and Troncoso, Juan and Moreno, Fermin and Nohr, Ellen A. and Sørensen, Thorkild I. A. and Heutink, Peter and Sánchez-Juan, Pascual and Posthuma, Danielle and Coppola, Giovanni and Clarimón, Jordi and Christensen, Kaare and Ertekin-Taner, Nilüfer and Scholz, Sonja W. and Ramirez, Alfredo and Ruiz, Agustin and Slagboom, Eline and van der Flier, Wiesje M. and Holstege, Henne, A Nonsynonymous Mutation in PLCG2 Reduces the Risk of Alzheimer's Disease, Dementia with Lewy-Bodies and Frontotemporal Dementia, and Increases the Likelihood of Longevity (December 21, 2018). Available at SSRN: https://ssrn.com/abstract=3307650

Sven J. Van der Lee

VU University Amsterdam

De Boelelaan 1105
Amsterdam, ND North Holland 1081 HV
Netherlands

Olivia J. Conway

Mayo Clinic - Florida

4500 San Pablo Rd S
Jacksonville, FL 32224
United States

Iris Jansen

VU University Amsterdam - Department of Neurology

Amsterdam
Netherlands

Minerva M. Carrasquillo

Mayo Clinic - Florida

4500 San Pablo Rd S
Jacksonville, FL 32224
United States

Luca Kleineidam

University of Cologne - Division of Neurogenetics and Molecular Psychiatry

Kerpener Strasse 62
Cologne, 50924
Germany

Erik van den Akker

Leiden University - Medical Center (LUMC)

Albinusdreef 2
Leiden, South Holland 2333 ZA
Netherlands

Isabel Hernández

Universitat Internacional de Catalunya

Immaculada 22
Barcelona, 08017
Spain

Kristel R. Van Eijk

Utrecht University - Department of Neurology

GA Utrecht
Netherlands

Najada Stringa

VU University Amsterdam - Amsterdam Public Health Research Institute

Amsterdam
Netherlands

Jason A. Chen

University of California, Los Angeles (UCLA)

405 Hilgard Avenue
Box 951361
Los Angeles, CA 90095
United States

Anna Zettergren

Göteborg University

Viktoriagatan 30
Göteborg, 405 30
Sweden

Till F. M. Andlauer

Max Planck Institute of Psychiatry

Munich
Germany

Monica Diez-Fairen

Hospital Universitario Mutua de Terrassa

Barcelona
Spain

Javier Simon-Sanchez

German Center for Neurodegenerative Diseases (DZNE)

von Siebold Strasse 3a
Goettingen, 37075
Germany

Alberto Lleó

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Madrid
Spain

Henrik Zetterberg

Göteborg University - Institute of Neuroscience and Physiology

PO Box 430
Göteborg, SE405 30
Sweden

Marianne Nygaard

University of Southern Denmark

Campusvej 55
DK-5230 Odense, 5000
Denmark

Cornelis Blauwendraat

Government of the United States of America - National Institute of Neurological Disorders and Stroke (NINDS)

9000 Rockville Pike
Bethesda, MD 20892
United States

Jeanne E. Savage

VU University Amsterdam

De Boelelaan 1105
Amsterdam, ND North Holland 1081 HV
Netherlands

Jonas Mengel-From

University of Southern Denmark

Campusvej 55
DK-5230 Odense, 5000
Denmark

Sonia Moreno-Grau

Universitat Internacional de Catalunya

Immaculada 22
Barcelona, 08017
Spain

Michael Wagner

Bonn University

Meckenheimer Allee 166
Bonn, D-53115
Germany

Juan Fortea

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Madrid
Spain

Michael J. Keogh

University of Newcastle

5 Barrack Road
Devonshire Building
NEWCASTLE UPON TYNE, NE1 7RU
United Kingdom

Kaj Blennow

Göteborg University - Institute of Neuroscience and Physiology

PO Box 430
Göteborg, SE405 30
Sweden

Göteborg University - Sahlgrenska University Hospital

PO Box 400
Göteborg, SE405 30
Sweden

Ingmar Skoog

Göteborg University

Viktoriagatan 30
Göteborg, 405 30
Sweden

Manuel A. Friese

German Competence Network Multiple Sclerosis (KKNMS)

Germany

Olga Pletnikova

Johns Hopkins University - School of Medicine

733 North Broadway
Suite G-49
Baltimore, MD 21205-2196
United States

Miren Zulaica

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Madrid
Spain

Carmen Lage

affiliation not provided to SSRN

Itziar De Rojas

Carlos III Institute of Health

c/ Monforte de Lemos 5
Madrid, Madrid 28029
Spain

Steffi Riedel-Heller

University of Leipzig - Institute for Social Medicine, Occupational Health and Public Health

Leipzig, 04103
Germany

Ignacio Illán-Gala

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Madrid
Spain

Wei Wei

University of Cambridge

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

Bernard Jeune

University of Southern Denmark

Campusvej 55
DK-5230 Odense, 5000
Denmark

Adela Orellana

Universitat Internacional de Catalunya

Immaculada 22
Barcelona, 08017
Spain

Florian Then Bergh

German Competence Network Multiple Sclerosis (KKNMS)

Germany

Xue Wang

Mayo Clinic - Florida

4500 San Pablo Rd S
Jacksonville, FL 32224
United States

Marc Hulsman

VU University Amsterdam - Department of Neurology

Amsterdam
Netherlands

Nina Beker

VU University Amsterdam

De Boelelaan 1105
Amsterdam, ND North Holland 1081 HV
Netherlands

Niccolo Tesí

VU University Amsterdam

De Boelelaan 1105
Amsterdam, ND North Holland 1081 HV
Netherlands

Christopher Morris

University of Newcastle

5 Barrack Road
Devonshire Building
NEWCASTLE UPON TYNE, NE1 7RU
United Kingdom

Begoña Indakoetxea

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Madrid
Spain

Lyduine E. Collij

VU University Medical Center

De Boelelaan 1117
Amsterdam, North Holland 1081 HV
Netherlands

Martin Scherer

University Medical Center Hamburg-Eppendorf

Martinistrasse 52
Hamburg, 20246
Germany

Estrella Morenas-Rodríguez

Utrecht University - University Medical Center (Utrecht)

6.119, PO Box 85500
Utrecht, 3508 GA
Netherlands

James W. Ironside

University of Edinburgh

Old College
South Bridge
Edinburgh, Scotland EH8 9JY
United Kingdom

Bart. N.M. van Berckel

VU University Medical Center

De Boelelaan 1117
Amsterdam, North Holland 1081 HV
Netherlands

Daniel Alcolea

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Madrid
Spain

Heinz Wiendl

German Competence Network Multiple Sclerosis (KKNMS)

Germany

Samantha L. Strickland

Mayo Clinic - Florida

4500 San Pablo Rd S
Jacksonville, FL 32224
United States

Pau Pastor

Hospital Universitario Mutua de Terrassa

Barcelona
Spain

Eloy Rodríguez Rodríguez

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Madrid
Spain

Bradley F. Boeve

Mayo Clinic

200 First Street SW
Rochester, MN (507) 284-2511 55905
United States

Ronald C. Petersen

Mayo Clinic

200 First Street SW
Rochester, MN (507) 284-2511 55905
United States

Tanis J. Ferman

Mayo Clinic - Florida

4500 San Pablo Rd S
Jacksonville, FL 32224
United States

Jay A. van Gerpen

Mayo Clinic - Florida

4500 San Pablo Rd S
Jacksonville, FL 32224
United States

Marcel J. T. Reinders

Delft University of Technology

Stevinweg 1
Stevinweg 1
Delft, 2628 CN
Netherlands

Ryan J. Uitti

Mayo Clinic - Florida

4500 San Pablo Rd S
Jacksonville, FL 32224
United States

Lluis Tarraga

Universitat Internacional de Catalunya

Immaculada 22
Barcelona, 08017
Spain

Wolfgang Maier

University of Bonn - Department of Neurodegenerative Disease and Gerontopsychiatry

Bonn, 53127
Germany

Oriol Dols-Icardo

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Madrid
Spain

Amit Kawalia

University Hospital of Cologne

Building 47, 9th floor Kerpener Str.
Herderstrasse 52
Cologne, 50931
Germany

Maria Carolina Dalmasso

University Hospital of Cologne

Building 47, 9th floor Kerpener Str.
Herderstrasse 52
Cologne, 50931
Germany

Mercè Boada

Universitat Internacional de Catalunya

Immaculada 22
Barcelona, 08017
Spain

Uwe K. Zettl

German Competence Network Multiple Sclerosis (KKNMS)

Germany

Natasja M. Van Schoor

University of Amsterdam - Amsterdam Public Health Research Institute

Meibergdreef 9
Amsterdam, 1105
Netherlands

Marian Beekman

Leiden University - Section of Molecular Epidemiology

Netherlands

Mariet Allen

Mayo Clinic - Florida

4500 San Pablo Rd S
Jacksonville, FL 32224
United States

Eliezer Masliah

National Institutes of Health (NIH)

9000 Rockville Pike
Bethesda, MD 20892
United States

Adolfo López de Munain

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Madrid
Spain

Alexander Pantelyat

Johns Hopkins University - School of Medicine

733 North Broadway
Suite G-49
Baltimore, MD 21205-2196
United States

Zbigniew K. Wszolek

Mayo Clinic - Florida

4500 San Pablo Rd S
Jacksonville, FL 32224
United States

Owen A. Ross

Mayo Clinic - Florida

4500 San Pablo Rd S
Jacksonville, FL 32224
United States

Dennis W. Dickson

Mayo Clinic - Florida

4500 San Pablo Rd S
Jacksonville, FL 32224
United States

Neill R. Graff-Radford

Mayo Clinic - Florida

4500 San Pablo Rd S
Jacksonville, FL 32224
United States

David Knopman

Mayo Clinic

200 First Street SW
Rochester, MN (507) 284-2511 55905
United States

Rosa Rademakers

Mayo Clinic - Florida - Department of Neuroscience

4500 San Pablo Rd S
Jacksonville, 32224
United States

Afina W. Lemstra

VU University Amsterdam

De Boelelaan 1105
Amsterdam, ND North Holland 1081 HV
Netherlands

Yolande A. L. Pijnenburg

VU University Amsterdam

De Boelelaan 1105
Amsterdam, ND North Holland 1081 HV
Netherlands

Philip Scheltens

VU University Amsterdam - Department of Neurology

Amsterdam
Netherlands

Thomas Gasser

University of Tuebingen

Wilhelmstr. 19
72074 Tuebingen, Baden Wuerttemberg 72074
Germany

Patrick F. Chinnery

University Medical Center Hamburg-Eppendorf

Martinistrasse 52
Hamburg, D - 20246
Germany

Bernhard Hemmer

Technische Universität München (TUM)

Arcisstrasse 21
Munich, 80333
Germany

Martijn A. Huisman

VU University Amsterdam - Amsterdam Public Health Research Institute

Amsterdam
Netherlands

Juan Troncoso

Johns Hopkins University - Department of Pathology

Baltimore, MD 21231
United States

Fermin Moreno

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Madrid
Spain

Ellen A. Nohr

University of Southern Denmark - Institute of Clinical Research

Campusvej 55
DK-5230 Odense, 5000
Denmark

Thorkild I. A. Sørensen

University of Copenhagen - Section of Metabolic Genetics

Blegdamsvej 3B
Copenhagen, DK-2200
Denmark

Peter Heutink

German Center for Neurodegenerative Diseases (DZNE)

von Siebold Strasse 3a
Goettingen, 37075
Germany

Pascual Sánchez-Juan

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Madrid
Spain

Danielle Posthuma

VU University Medical Center

De Boelelaan 1117
Amsterdam, North Holland 1081 HV
Netherlands

Giovanni Coppola

University of California, Los Angeles (UCLA) - Department of Neurology

1000 Veteran Avenue, Box 956939
Los Angeles, CA 90095-6939
United States

Jordi Clarimón

Centro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED)

Madrid
Spain

Kaare Christensen

University of Southern Denmark

Campusvej 55
DK-5230 Odense, 5000
Denmark

Nilüfer Ertekin-Taner

VU University Amsterdam

De Boelelaan 1105
Amsterdam, ND North Holland 1081 HV
Netherlands

Sonja W. Scholz

National Institutes of Health - Neurodegenerative Diseases Research Unit

Bethesda, MD
United States

Alfredo Ramirez

University of Cologne - Division of Neurogenetics and Molecular Psychiatry ( email )

Kerpener Strasse 62
Cologne, 50924
Germany

University of Bonn - Department of Neurodegenerative Disease and Gerontopsychiatry ( email )

Bonn, 53127
Germany

Agustin Ruiz

Universitat Internacional de Catalunya

Immaculada 22
Barcelona, 08017
Spain

Eline Slagboom

Leiden University - Medical Center (LUMC)

Albinusdreef 2
Leiden, 2333 ZA
Netherlands

Wiesje M. Van der Flier

University of Bonn - Institute of Innate Immunity

Bonn
Germany

Henne Holstege (Contact Author)

VU University Amsterdam - Alzheimer Center Amsterdam ( email )

Amsterdam
Netherlands

VU University Amsterdam - Department of Clinical Genetics ( email )

Amsterdam
Netherlands

No contact information is available for DESGESCO Dementia Genetics Spanish Consortium
No contact information is available for Alzheimer Disease European DNA Biobank
No contact information is available for IFGC International FTD-Genomics Consortium
No contact information is available for IPDGC The International Parkinson Disease Genomics Consortium
No contact information is available for RiMod-FTD Rsk and Modifying factors in Fronto-Temporal Dementia
No contact information is available for Netherlands Brain Bank (NBB)

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