Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Abstract summary

Large-scale whole-genome sequencing and exome sequencing study identified rare protective variants in PLCG2 and ABI3 and confirmed TREM2 coding variants as Alzheimer's disease risk factors. Established PLCG2 P522R as a hypermorphic protective variant enhancing microglial immune function. Highlighted the convergent microglial immune pathway in AD genetics.

Evidence labels

Therapeutic relevance

Established PLCG2 as a protective genetic target; PLCG2 activation mimicry is a potential therapeutic approach for AD.