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000140840 1001_ $$0P:(DE-HGF)0$$avan der Lee, Sven J$$b0$$eCorresponding author
000140840 245__ $$aA nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.
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000140840 520__ $$aThe 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.
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000140840 650_2 $$2MeSH$$aAlleles
000140840 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000140840 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: genetics
000140840 650_2 $$2MeSH$$aBrain: immunology
000140840 650_2 $$2MeSH$$aBrain: metabolism
000140840 650_2 $$2MeSH$$aBrain: pathology
000140840 650_2 $$2MeSH$$aDementia: genetics
000140840 650_2 $$2MeSH$$aFrontotemporal Dementia: genetics
000140840 650_2 $$2MeSH$$aGenetic Predisposition to Disease
000140840 650_2 $$2MeSH$$aGenome-Wide Association Study
000140840 650_2 $$2MeSH$$aHumans
000140840 650_2 $$2MeSH$$aLewy Body Disease: genetics
000140840 650_2 $$2MeSH$$aLongevity: genetics
000140840 650_2 $$2MeSH$$aMicroglia: metabolism
000140840 650_2 $$2MeSH$$aMultiple Sclerosis: genetics
000140840 650_2 $$2MeSH$$aMutation
000140840 650_2 $$2MeSH$$aNeuroimaging
000140840 650_2 $$2MeSH$$aParkinson Disease: genetics
000140840 650_2 $$2MeSH$$aPhospholipase C gamma: genetics
000140840 650_2 $$2MeSH$$aRisk
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