PLCG2as a Risk Factor for Alzheimer’s Disease

AbstractAlzheimer’s disease (AD) is characterized by robust microgliosis and phenotypic changes that accompany disease pathogenesis. Indeed, genetic variants in microglial genes are linked to risk for AD. Phospholipase Cγ2 (PLCG2) participates in the transduction of signals emanating from immune cell-surface receptors that regulate the inflammatory response and is selectively expressed by microglia in the brain. A rare variant inPLCG2(P522R) was previously found to be protective against AD, indicating thatPLCG2may play a role in AD pathophysiology. Here, we report that a rare missense variant inPLCG2confers increased AD risk (p=0.047; OR=1.164 [95% CI=1.002-1.351]). Additionally, we observed thatPLCG2expression levels are increased in several brain regions of AD patients, correlating with brain amyloid deposition. This provides further evidence thatPLCG2may play an important role in AD pathophysiology. Together, our findings indicate thatPLCG2is a potential new therapeutic target for AD.