Myeloid Cells 2 (TREM2) and Innate Immunity

Mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been identified as risk factors for late-onset Alzheimer's disease (AD). In the central nervous system, TREM2 is expressed primarily in microglia, and shown to play important roles in controlling neuroinflammatory events including phagocytosis and production of pro-inflammatory cytokines. A recent paper from Dr. Bu's lab reported that apoE is a ligand for microglial TREM2. Binding of apoE to TREM2 increased phagocytosis of apoptotic neurons by microglia.

This study suggests that the interaction between apoE and TREM2 likely regulates phagocytosis of dying cells and neural debris. Importantly, this observation implicates a novel pathway in which the two strongest genetic links to late-onset AD are able to physically interact to modulate microglial function in AD. Further work in the lab seeks to clarify the functional consequence of impaired apoE binding via the AD-associated TREM2-R47H mutation and the role TREM2-mediated neuroinflammatory events play in the neurodegenerative process using biochemical approaches, primary mouse microglia cultures, iPSC-derived myeloid cells, and animal models.