PLCG2 modulates TREM2 expression and signaling in response to Alzheimer's disease pathology.

ABSTRACT:

Background

Phospholipase C gamma 2 (PLCG2) is an intracellular effector of microglial cell surface receptors, including triggering receptor expressed on myeloid cells 2 (TREM2). Variants which alter PLCG2 activity impact Alzheimer's disease (AD) risk, but the effects of PLCG2 deficiency in AD remain unclear.

Methods

5xFAD mice were crossed with PLCG2- and TREM2-deficient mice to assess the role of PLCG2 in response to amyloid pathology. Human bulk RNA-sequencing data were used to validate findings in AD patients.

Results

In 5xFAD mice, the absence of PLCG2 resulted in reduced TREM2 expression and impaired microglial associations with amyloid beta plaques. Transcriptomic analysis revealed perturbations in immune-related pathways shared between PLCG2 and TREM2 deficienc

SUBMITTER: Messenger EJ 

PROVIDER: S-EPMC12064341 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature