Journal
ACTA NEUROPATHOLOGICA
Volume 138, Issue 2, Pages 237-250Publisher
SPRINGER
DOI: 10.1007/s00401-019-02026-8
Keywords
Alzheimer's disease; Frontotemporal dementia; Dementia with Lewy bodies; Progressive supranuclear palsy; Parkinson's disease; Amyotrophic lateral sclerosis; Multiple sclerosis; Neurodegenerative disease; Longevity; PLCG2; Phospholipase C Gamma 2
Categories
Funding
- Amsterdam dementia Cohort (ADC): Research of the Alzheimer center Amsterdam
- Stichting Alzheimer Nederland [WE09.2014-03]
- Stichting VUmc fonds
- Stichting Dioraphte [JPco-fuND FP-829-029, 733051061]
- Stichting Diorapthe, horstingstuit foundation, Memorabel (ZonMW) [733050814]
- Stichting VUmc Fonds [JPco-fuND FP-829-029, 733051061]
- German Study on Ageing, Cognition and Dementia in Primary Care Patients
- German Research Network on Degenerative Dementia
- Health Service Research Initiative
- (AgeQualiDe) - German Federal Ministry of Education and Research [KND: 01GI0102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 01GI0434, KNDD: 01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716, 01GY1322A, 01GY1322B, 01GY1322C, 01GY1322D, 01GY1322E, 01GY1322F, 01GY1322G]
- Innovative Medicines Initiative 2 Joint Undertaking [115975]
- UK Medical Research Council [13044]
- UK NIHR
- Medical Research Council Mitochondrial Biology Unit [MC_UU_00015/9]
- National Institute for Health Research (NIHR) Biomedical Research Centre based at Cambridge University Hospitals NHS Foundation Trust
- University of Cambridge
- National Program for Research Infrastructure [09-063256]
- Danish Agency for Science Technology and Innovation
- Velux Foundation
- US National Institute of Health [P01 AG08761]
- Danish Agency for Science, Technology and Innovation/The Danish Council for Independent Research [11-107308]
- European Union [259679]
- INTERREG 4 A programme Syddanmark-Schleswig-K.E.R.N.
- EU
- (European Regional Development Fund)
- CERA Foundation (Lyon)
- AXA Research Fund
- Health Foundation (Helsefonden), Copenhagen, Denmark
- Danish Obesity Research Centre (DanORC)
- MRC centre for Causal Analyses in Translational Epidemiology (MRC CAiTE) - Wellcome Trust [WT 084762]
- GOYA
- Danish National Research Foundation
- Pharmacy Foundation
- Egmont Foundation
- March of Dimes Birth Defects Foundation
- Augustinus Foundation
- Health Foundation
- Fundacio ACE (FACE)
- Fundacio ACE research programs
- Fundacio ACE collaborates with the Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain)
- EU/EFPIA Innovative Medicines Initiative Joint Undertaking ADAPTED [115975, PI13/02434, PI16/01861]
- Accion Estrategica en Salud, integrated in the Spanish National R + D + I Plan
- ISCIII (Instituto de Salud Carlos III)-Subdireccion General de Evaluacion
- Fondo Europeo de Desarrollo Regional (FEDER-Una manera de Hacer Europa)
- Fundacion bancaria La Caixa
- Genetics of Healthy Ageing Study (GEHA - NL)
- EU GEHA Project [LSHM-CT-2004-503-270]
- Stena Foundation
- Swedish Research Council [2015-02830, 2013-8717]
- Swedish Research Council for Health, Working Life and Wellfare [2013-1202, 2005-0762, 2008-1210, 2013-2300, 2013-2496, 2013-0475]
- Brain Foundation
- Sahlgrenska University Hospital (ALF)
- Alzheimer's Association [IIRG-03-6168]
- Alzheimer's Association Zenith Award [ZEN-01-3151]
- Eivind och Elsa K: son Sylvans Stiftelse
- Swedish Alzheimer Foundation
- IPDGC (The International Parkinson Disease Genomics Consortium)
- Kompetenznetz Multiple Sklerose (KKNMS)
- German Ministry for Education and Research (BMBF) as part of the German Competence Network Multiple Sclerosis (KKNMS) [01GI0916, 01GI0917]
- Munich Cluster for Systems Neurology (SyNergy)
- BMBF through the Integrated Network IntegraMent, under the auspices of the e: Med Programme [01ZX1614J]
- EU Horizon 2020 project MultipleMS
- Netherlands Ministry of Health, Welfare and Sports, Directorate of Long-Term Care
- Innovation-Oriented Research Program on Genomics [SenterNovem IGE05007]
- Netherlands Consortium for Healthy Ageing [050-060-810]
- Georg Forster Research Award (Alexander von Humboldt Foundation)
- Mayo Clinic AD
- National Institute on Aging [ZIA-NS003154, Z01-AG000949]
- National Institute of Neurological Disorders and Stroke [R01 NS080820, P50 NS072187]
- Mayo Clinic is a Lewy Body Dementia Association (LBDA) Research Center of Excellence
- American Parkinson Disease Association (APDA) Information and Referral Center [U54-NS100693]
- Little Family Foundation
- Mangurian Foundation
- NINDS [R01 NS078086]
- Mayo Clinic Center for Regenerative Medicine, Mayo Clinic Center for Individualized Medicine, Mayo Clinic Neuroscience Focused Research Team (Cecilia and Dan Carmichael Family Foundation)
- James C. and Sarah K. Kennedy Fund
- Sol Goldman Charitable Trust
- CurePSP| Society
- Tau Consortium
- National Institutes of Health [U19-AG03365, P50 NS38377, P50-AG005146]
- Johns Hopkins Morris K. Udall Center of Excellence for Parkinson's Disease Research [NIH P50 NS38377]
- Johns Hopkins Alzheimer's Disease Research Center
- NIMH
- NINDS Human Genetics Resource Center DNA
- Virginia Commonwealth University Brain Bank
- Georgetown University Brain Bank
- University of Miami
- Intramural Research Program of the NIH National Institute of Neurological Disorders and Stroke
- Fondo de Investigaciones Sanitarias-Fondos FEDER EuropeanUnion [PI15/00878]
- CIBERNED
- Carlos III Institute of Health, Spain [PI08/0139, PI12/02288, PI16/01652]
- Fondo Europeo de Desarrollo Regional (FEDER), Union Europea, Una manera de hacer Europa
- ALS Foundation Netherlands
- MND association (UK) - Generalitat de Catalunya [2017 SGR 547]
- Institute of Health Carlos III-Subdireccion General de Evaluacion
- Fondo Europeo de Desarrollo Regional (FEDER- Una manera de Hacer Europa) [PI11/02526, PI14/01126, PI17/01019, PI17/01895]
- Centro de Investigacion Biomedica en Red Enfermedades Neurodegenerativas programme
- Alzheimer Disease
- Fundacio Bancaria Obra Social La Caixa (DABNI project)
- Fundacion BBVA
- Biodonostia HRI Genomics Platform
- Fundacion Salud [PI2013156]
- Diputacion Foral de Gipuzkoa [114/17]
- Netherlands Organization for Scientific Research [NWO VICI 453-14-005, NWO: 480-05-003]
- VU University, Amsterdam, The Netherlands
- Dutch Brain Foundation
- Dutch National Computing and Networking Services SurfSARA [16406]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [ZIANS003154] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [ZIAAG000936] Funding Source: NIH RePORTER
- MRC [MC_UU_00015/9, G1100540, MC_UU_00015/8, G0900580] Funding Source: UKRI
Ask authors/readers for more resources
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 PLC gamma 2 pathway as drug-target.
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