Abstract Body

In Alzheimer disease (AD) models, microglia appear to influence amyloid-β (Aβ) linked tau seeding and spreading. We have been studying the effects of microglia, genes expressed by microglia, and genes expressed by microglia and other cells on Aβ-linked tau seeding and spreading. In the context of Aβ depositon, we asked whether microglial removal as well as removal with repopulation decreased Aβ driven tau seeding and spreading. We found that both TREM2 KO and microglial ablation dramatically enhance tau seeding and spreading around plaques. Interestingly, although repopulated microglia clustered around plaques, they had a reduction in disease associated microglia (DAM) gene expression and elevated tau seeding/spreading. Together, these data suggest that TREM2-dependent activation of the DAM phenotype is essential in delaying Aβ-induced pathological tau propagation. We are in the process of determining the role of apoE generally and apoE specifically deposited in plaques on Aβ-induced tau seeding and spreading.