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Neurobiol Aging. 2019 Jul 2;81:234-243. doi: 10.1016/j.neurobiolaging.2019.06.008. [Epub ahead of print]

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

Author information

1
Douglas Hospital Research Centre, Montréal, Canada; Centre for the Studies on the Prevention of Alzheimer's Disease, Montréal, Canada; McGill University, Montréal, Canada.
2
Douglas Hospital Research Centre, Montréal, Canada; Centre for the Studies on the Prevention of Alzheimer's Disease, Montréal, Canada.
3
McGill University and Génome Québec Innovation Centre, Montréal, Canada.
4
Douglas Hospital Research Centre, Montréal, Canada; Centre for the Studies on the Prevention of Alzheimer's Disease, Montréal, Canada; McGill University, Montréal, Canada. Electronic address: judes.poirier@mcgill.ca.

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.

KEYWORDS:

APOE4; Alzheimer's disease; Genome-wide association study; PPP2R1A; Quebec Founder Population; Visuospatial performance

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