Microglia‐specific Alzheimer's disease polygenic risk score predicts longitudinal increase in plasma tau and faster cognitive decline in cognitively unimpaired older adults

Our findings suggest AD heritability localizing to microglial genes and contribute to increased soluble pTau217 release at a given Aβ burden, which in turn mediates the association between microglial AD genetic risk and cognitive decline. Our results are consistent with previous studies implying microglia in Aβ-related tau accumulation and indicate that much of microglial impact on cognitive decline may occur through accelerated tau pathology in CU older adults.