The Microglial membrane receptor TREM2 mediates exosome secretion to promote phagocytosis of amyloid-β by microglia.

Considerable evidence links the microglial transmembrane receptor TREM2 to the progression of Alzheimer's disease through its involvement in Aβ phagocytosis by microglia. While previous studies have mainly focused on the phagocytic regulation of microglia itself, the antigen presentation of microglial exosomes in the process of immunity has been less investigated. Here, we identified TREM2 expressed on the membrane of microglial exosomes and found that it controlled exosome secretion without affecting exosome size. Microglial exosomes bind to Aβ in a TREM2-dependent manner, which changes the inflammatory environment around Aβ and promotes microglia to phagocytose Aβ. These findings delineate a novel exosome-mediated mechanism of microglial cell-Aβ crosstalk that facilitates Aβ clearance under either physiological or pathological conditions in the central nervous system.