Fig. 5.

Function of TREM2 in AD. TREM2 expression enhances the proliferation and migration of microglia, and improves the phagocytosis ability. At the early stage of AD development, TREM2 expression microglia surround the Aβ plaque, interact with lipidated Aβ to efficiently clear them. The surrounding microglia also prevent the spread of Aβ. But at the late stage of AD, TREM2 expression microglia fail to clear the aggregates, leading to chronic inflammation, which then attenuates the phagocytosis ability of microglia, induces tau phosphorylation and aggregation. For individuals with TREM2 mutation, the affinity of TREM2 was weakened, which inhibits the proliferation and migration of microglia, leading to the failure of microglia surrounding Aβ aggregates. TREM2 mutation also enhance the secretion of cytokines from microglia. As a result, TREM2 mutation in microglia benefits the spread of Aβ, and the phosphorylation and aggregation of tau, exacerbating AD pathology