Heterozygous expression of the Alzheimer's disease-protective PLCγ2 P522R variant enhances Aβ clearance while preserving synapses.

ABSTRACT:

Background

A rare coding variant, P522R, in the phospholipase C gamma 2 (PLCG2) gene has been identified as protective against late-onset Alzheimer's disease (AD), but the mechanism is unknown. PLCG2 is exclusively expressed in microglia within the central nervous system, and altered microglial function has been implicated in the progression of AD.

Methods

Healthy control hiPSCs were CRISPR edited to generate cells heterozygous and homozygous for the PLCG2^P522R variant. Microglia derived from these hiPSC's were used to investigate the impact of PLCγ2^P522R on disease relevant processes, specifically microglial capacity to take up amyloid beta (Aβ) and synapses. Targeted qPCR assessment was conducted to explore expression changes in core AD linked and mic

SUBMITTER: Solomon S 

PROVIDER: S-EPMC9329165 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature