The Alzheimer's disease-associated protective Plcγ2-P522R variant promotes immune functions.

ABSTRACT:

Background

Microglia-specific genetic variants are enriched in several neurodegenerative diseases, including Alzheimer's disease (AD), implicating a central role for alterations of the innate immune system in the disease etiology. A rare coding variant in the PLCG2 gene (rs72824905, p.P522R) expressed in myeloid lineage cells was recently identified and shown to reduce the risk for AD.

Methods

To assess the role of the protective variant in the context of immune cell functions, we generated a Plcγ2-P522R knock-in (KI) mouse model using CRISPR/Cas9 gene editing.

Results

Functional analyses of macrophages derived from homozygous KI mice and wild type (WT) littermates revealed that the P522R variant potentiates the primary function of Plcγ2 as a Pip2-metabolizing enzyme.

SUBMITTER: Takalo M 

PROVIDER: S-EPMC7488484 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature