Association of PPP2R1A with Alzheimer's disease and specific cognitive domains.
|Title||Association of PPP2R1A with Alzheimer's disease and specific cognitive domains.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Miron J, Picard C, Labonte A, Auld D, Breitner J, Poirier J|
|Corporate Authors||United Kingdom Brain Expression Consortium, PREVENT-AD Research Group|
|Date Published||2019 Jul 02|
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.
|Alternate Journal||Neurobiol. Aging|