PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment.

ABSTRACT: A rare coding variant (rs72824905, p.P522R) conferring protection against Alzheimer's disease (AD) was identified in the gene encoding the enzyme phospholipase-C-γ2 (PLCG2) that is highly expressed in microglia. To explore the protective nature of this variant, we employed latent process linear mixed models to examine the association of p.P522R with longitudinal cognitive decline in 3595 MCI patients, and in 10,097 individuals from population-based studies. Furthermore, association with CSF levels of pTau₁₈₁, total tau, and Aβ_1-42 was assessed in 1261 MCI patients. We found that MCI patients who carried the p.P522R variant showed a slower rate of cognitive decline compared to non-carriers and that this effect was mediated by lower pTau₁₈₁ levels in CSF. The

SUBMITTER: Kleineidam L 

PROVIDER: S-EPMC7244617 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature