Association of PPP2R1A with Alzheimer's disease and specific cognitive domains.

TitleAssociation of PPP2R1A with Alzheimer's disease and specific cognitive domains.
Publication TypeJournal Article
Year of Publication2019
AuthorsMiron J, Picard C, Labonte A, Auld D, Breitner JCS, Poirier J
Corporate AuthorsUnited Kingdom Brain Expression Consortium, PREVENT-AD Research Group
JournalNeurobiol Aging
Volume81
Pagination234-243
Date Published2019 09
ISSN1558-1497
Abstract

In an attempt to identify novel genetic variants associated with sporadic Alzheimer's disease (AD), a genome-wide association study was performed on a population isolate from Eastern Canada, referred to as the Québec Founder Population (QFP). In the QFP cohort, the rs10406151 C variant on chromosome 19 is associated with higher AD risk and younger age at AD onset in APOE4- individuals. After surveying the region surrounding this intergenic polymorphism for brain cis-eQTL associations in BRAINEAC, we identified PPP2R1A as the most likely target gene modulated by the rs10406151 C variant. PPP2R1A mRNA and protein levels are elevated in multiple regions from QFP autopsy-confirmed AD brains when compared with age-matched controls. Using an independent cohort of cognitively normal individuals with a parental history of AD, we found that the rs10406151 C variant is significantly associated with lower visuospatial and constructional performances. The association of the rs10406151 C variant with AD risk appears to involve brain PPP2R1A gene expression alterations. However, the exact pathological pathway by which this variant modulates AD remains elusive.

DOI10.1016/j.neurobiolaging.2019.06.008
Alternate JournalNeurobiol. Aging
PubMed ID31349112
Grant ListMOP-119321 / / CIHR / Canada