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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 PLC?2 pathway as drug-target.
Fuente: Acta Neuropathologica, 2019, 138(2), 237-250
Editorial: Springer Verlag
Año de publicación: 2019
Nº de páginas: 14
Tipo de publicación: Artículo de Revista
DOI: 10.1007/s00401-019-02026-8
ISSN: 0001-6322,1432-0533
Url de la publicación: https://doi.org/10.1007/s00401-019-02026-8
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LEE, SVEN J. VAN DER
CONWAY, OLIVIA J.
JANSEN, IRIS
CARRASQUILLO, MINERVA M.
KLEINEIDAM, LUCA
AKKER, ERIK VAN DEN
HERNÁNDEZ, ISABEL
EIJK, KRISTEL R. VAN
STRINGA, NAJADA
CHEN, JASON A.
ZETTERGREN, ANNA
ANDLAUER, TILL F. M.
DIEZ FAIREN, MONICA
SIMON SANCHEZ, JAVIER
LLEÓ, ALBERTO
ZETTERBERG, HENRIK
NYGAARD, MARIANNE
BLAUWENDRAAT, CORNELIS
SAVAGE, JEANNE E.
PASCUAL SANCHEZ JUAN
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