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

United Kingdom Brain Expression Consortium, PREVENT-AD Research Group

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)234-243
Number of pages10
JournalNeurobiology of aging
StatePublished - Sep 2019


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

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology


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