Evidence map›Paper›PMID 31131421›Full record

ArticleActa neuropathologica2019

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.

Sven J van der Lee, Olivia J Conway, Iris Jansen, Minerva M Carrasquillo, Luca Kleineidam, Erik van den Akker, Isabel Hernández, Kristel R van Eijk, Najada Stringa, Jason A Chen and 98 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
9.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 129 citations in OpenAlex.

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  12. A novel approach to resilience and its links with education and Alzheimer's disease genetics.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
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12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

108 authors at 20 institutions in 8 countries.

Sven J van der LeeAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands. s.j.vanderlee@amsterdamumc.nl.ORCID http://orcid.org/0000-0003-1606-8643
Olivia J ConwayDepartment of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Iris JansenAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Minerva M CarrasquilloDepartment of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Luca KleineidamDepartment for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, Germany.
Erik van den AkkerMolecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Isabel HernándezResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
Kristel R van EijkDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
Najada StringaAmsterdam UMC-Vrije Universiteit Amsterdam, Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
Jason A ChenInterdepartmental Program in Bioinformatics, University of California, Los Angeles, USA.
Anna ZettergrenNeuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Centre for Ageing and Health (AgeCap) at the University of Gothenburg, Gothenburg, Sweden.
Till F M AndlauerMax Planck Institute of Psychiatry, Munich, Germany.ORCID http://orcid.org/0000-0002-2917-5889
Monica Diez-FairenMovement Disorders and Memory Unit, Department of Neurology, University Hospital Mutua de Terrassa, Barcelona, Spain.
Javier Simon-SanchezGerman Center for Neurodegenerative Diseases (DZNE)-Tübingen, Tübingen, Germany.
Alberto LleóCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Henrik ZetterbergClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Marianne NygaardThe Danish Aging Research Center, Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Cornelis BlauwendraatNeurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, 20892-3707, USA.
Jeanne E SavageDepartment of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Jonas Mengel-FromEpidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Sonia Moreno-GrauResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
Michael WagnerDepartment for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, Germany.
Juan ForteaCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Michael J KeoghInstitute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
Kaj BlennowClinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Ingmar SkoogNeuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Centre for Ageing and Health (AgeCap) at the University of Gothenburg, Gothenburg, Sweden.
Manuel A FrieseGerman Competence Network Multiple Sclerosis (KKNMS), Munich, Germany.
Olga PletnikovaDepartment of Pathology (Neuropathology), Johns Hopkins University Medical Center, Baltimore, MD, USA.
Miren ZulaicaCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Carmen LageCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Itziar de RojasResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
Steffi Riedel-HellerInstitute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, Germany.
Ignacio Illán-GalaCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Wei WeiDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
Bernard JeuneEpidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Adelina OrellanaResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
Florian Then BerghGerman Competence Network Multiple Sclerosis (KKNMS), Munich, Germany.
Xue WangDepartment of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Marc HulsmanAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Nina BekerAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Niccolo TesiAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-1413-5091
Christopher M MorrisNewcastle Brain Tissue Resource, Edwardson Building, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
Begoña IndakoetxeaCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Lyduine E CollijDepartment of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Martin SchererDepartment of Primary Medical Care, Center for Psychosocial Medicine, University Medical Center, Hamburg-Eppendorf, Germany.
Estrella Morenas-RodríguezCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
James W IronsideCentre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Bart N M van BerckelDepartment of Radiology and Nuclear Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Daniel AlcoleaCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Heinz WiendlGerman Competence Network Multiple Sclerosis (KKNMS), Munich, Germany.
Samantha L StricklandDepartment of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Pau PastorMovement Disorders and Memory Unit, Department of Neurology, University Hospital Mutua de Terrassa, Barcelona, Spain.
Eloy Rodríguez RodríguezCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
DESGESCO (Dementia Genetics Spanish Consortium), EADB (Alzheimer Disease European DNA biobank)
EADB (Alzheimer Disease European DNA biobank)
IFGC (International FTD-Genomics Consortium), IPDGC (The International Parkinson Disease Genomics Consortium)
IPDGC (The International Parkinson Disease Genomics Consortium)
RiMod-FTD (Risk and Modifying factors in Fronto-Temporal Dementia)
Netherlands Brain Bank (NBB)
Bradley F BoeveDepartment of Neurology, Mayo Clinic Minnesota, Rochester, MN, 55905, USA.
Ronald C PetersenDepartment of Neurology, Mayo Clinic Minnesota, Rochester, MN, 55905, USA.
Tanis J FermanDepartment of Psychiatry and Psychology, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Jay A van GerpenDepartment of Neurology, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Marcel J T ReindersDelft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands.
Ryan J UittiDepartment of Neurology, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Lluís TárragaResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
Wolfgang MaierDepartment for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, Germany.
Oriol Dols-IcardoCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Amit KawaliaDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University Hospital Cologne, Cologne, Germany.
Maria Carolina DalmassoDivision of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine, University Hospital Cologne, Cologne, Germany.
Mercè BoadaResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
Uwe K ZettlGerman Competence Network Multiple Sclerosis (KKNMS), Munich, Germany.
Natasja M van SchoorAmsterdam UMC-Vrije Universiteit Amsterdam, Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
Marian BeekmanMolecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Mariet AllenDepartment of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Eliezer MasliahLaboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Adolfo López de MunainCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Alexander PantelyatDepartment of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, 21287, USA.
Zbigniew K WszolekDepartment of Neurology, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Owen A RossDepartment of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Neill R Graff-RadfordDepartment of Neurology, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
David KnopmanDepartment of Neurology, Mayo Clinic Minnesota, Rochester, MN, 55905, USA.
Rosa RademakersDepartment of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Afina W LemstraAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Yolande A L PijnenburgAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Philip ScheltensAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-1046-6408
Thomas GasserCenter of Neurology, Department of Neurodegenerative diseases, Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
Patrick F ChinneryDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
Bernhard HemmerDepartment of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Martijn A HuismanAmsterdam UMC-Vrije Universiteit Amsterdam, Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
Juan TroncosoDepartment of Pathology (Neuropathology), Johns Hopkins University Medical Center, Baltimore, MD, USA.
Fermin MorenoCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Ellen A NohrResearch Unit of Gynecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Thorkild I A SørensenNovo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Copenhagen, Denmark.
Peter HeutinkGerman Center for Neurodegenerative Diseases (DZNE)-Tübingen, Tübingen, Germany.
Pascual Sánchez-JuanCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Danielle PosthumaDepartment of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group
Jordi ClarimónCentro de Investigacion Biomedica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
Kaare ChristensenThe Danish Aging Research Center, Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Nilüfer Ertekin-TanerDepartment of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
Sonja W ScholzNeurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, 20892-3707, USA.
Alfredo RamirezDepartment for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, Bonn, Germany.
Agustín RuizResearch Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, Barcelona, Spain.
Eline SlagboomMolecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Wiesje M van der FlierAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Henne HolstegeAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands. h.holstege@amsterdamumc.nl.ORCID http://orcid.org/0000-0002-7688-3087
Biomedical Research Networking Center on Neurodegenerative Diseases · ESAmsterdam Neuroscience · NLUniversity of Southern Denmark · DKMayo Clinic in Florida · USUniversitat Autònoma de Barcelona · ESJohns Hopkins University · USMayo Clinic · USUniversity of Bonn · DEUniversity of Cambridge · GBSahlgrenska University Hospital · SEUniversität Hamburg · DEUniversity Hospital Mútua de Terrassa · ESGerman Center for Neurodegenerative Diseases · DELeiden University Medical Center · NLNational Institutes of Health · USUniversity Medical Center Utrecht · NLUniversity of California, Los Angeles · USAmsterdam University Medical Centers · NLCompetence Network Multiple Sclerosis · DEConsejo Nacional de Investigaciones Científicas y Técnicas · AR

Funding

Understanding Mechanisms of a-synuclein pathologyP50NS038377 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DAWSON, TED M. · 1998 to 2019
$38.8M
'T V ASSESSMENT - MEMORY DISORDERED PATIENTS'P50AG005146 · NIA · JOHNS HOPKINS UNIVERSITY · PI ALBERT, MARILYN S. · 1985 to 2019
$37.6M
Integrating the exposome and methylome to inform brain molecular changes in ADRD across established diverse cohorts.U01AG046139 · NIA · UNIVERSITY OF FLORIDA · PI ERTEKIN-TANER, NILUFER, FUNK, CORY · 2013 to 2022
$24.6M
TRAJECTORIES OF MORTALITY IN CAENORHABDITIS ELEGANSP01AG008761 · NIA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI ROACH, DEBORAH A · 1990 to 2008
$17.5M
Genetic characterization of atypical parkinsonismZIANS003154 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI SCHOLZ, SONJA · 2016 to 2025
$15.4M
Integrative translational discovery of vascular risk factors in aging and dementiaRF1AG051504 · NIA · MAYO CLINIC JACKSONVILLE · PI BU, GUOJUN, ERTEKIN-TANER, NILUFER · 2015 to 2019
$9.8M
Neuropathology CoreP50NS072187 · NINDS · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 2010 to 2017
$8.7M
Project 2: Identifying genes and Pathways that impact Tau Toxicity in FTDU54NS100693 · NINDS · MAYO CLINIC JACKSONVILLE · PI PETRUCELLI, LEONARD · 2016 to 2020
$6.2M
Harnessing Molecular Networks of Resilience for Therapeutic Discoveries in ADR01AG061796 · NIA · MAYO CLINIC JACKSONVILLE · PI ERTEKIN-TANER, NILUFER · 2018 to 2022
$5.7M
Neuroimmune responses and therapeutics of alpha-synucleinopathies of the aging populationZIAAG000936 · NIA · NATIONAL INSTITUTE ON AGING · PI COOKSON, MARK · 2017 to 2025
$4.1M
Genetic Discovery and Pathobiology of Frontotemporal Lobar Degeneration and Related TDP-43 ProteinopathiesR35NS097261 · NINDS · MAYO CLINIC JACKSONVILLE · PI RADEMAKERS, ROSA · 2017 to 2019
$2.9M
Genome wide SNP analysis in Parkinson's diseaseZ01AG000949 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW B · 2006 to 2008
$2.6M
EPA EP-C-14-005Intramural NIH HHS Z01 AG000949Intramural NIH HHS ZIA NS003154Medical Research Council 13044Medical Research Council G0900580Medical Research Council G1100540Medical Research Council MC_UU_00015/7Medical Research Council MC_UU_00015/8Medical Research Council MC_UU_00015/9NIA NIH HHS K23 AG059891NIA NIH HHS P01 AG008761NIA NIH HHS P50 AG005146NIA NIH HHS R01 AG061796NIA NIH HHS RF1 AG051504NIA NIH HHS U01 AG046139NINDS NIH HHS P50 NS038377NINDS NIH HHS P50 NS072187NINDS NIH HHS R01 NS078086NINDS NIH HHS R01 NS080820NINDS NIH HHS R35 NS097261NINDS NIH HHS U54 NS100693Wellcome TrustWellcome Trust 212219/Z/18/ZWellcome Trust WT 084762
6 · The paper itself

Abstract

The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.

Indexed as

MutationAllelesAlzheimer DiseaseAmyotrophic Lateral SclerosisBrainDementiaFrontotemporal DementiaGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLewy Body DiseaseLongevityMicrogliaMultiple SclerosisNeuroimagingParkinson DiseasePhospholipase C gammaPLCG2 protein, humanAlzheimer’s diseaseAmyotrophic lateral sclerosisDementia with Lewy bodiesFrontotemporal dementiaLongevityMultiple sclerosisNeurodegenerative diseaseParkinson’s diseasePhospholipase C Gamma 2PLCG2Progressive supranuclear palsy

Identifiers

PMID31131421
PMCPMC6660501
OpenAlexW2944923405

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