Microglia play a critical role as immune cells in the pathological regions of neurodegenerative diseases such as Alzheimer's disease (AD). This study elucidates that TREM2, present on the surface of microglia, recognizes and clears beta-amyloid associated with externalized phosphatidylserine (ePtdSer) during AD progression. Our findings highlight the pivotal role of the TREM2 receptor on microglia in identifying and eliminating beta-amyloid in conjunction with ePtdSer on neurons affected by AD. Specifically, the interaction between TREM2 and beta-amyloid is regulated by external factors, with ePtdSer playing a significant role. This new mechanism suggests that the presence of ePtdSer influences TREM2-dependent phagocytosis of microglia around amyloid plaques in AD. These insights offer promising directions for the development of immune cell-based therapeutic strategies targeting microglia in Alzheimer's disease.

more >> https://doi.org/10.1002/advs.202400064