TREM2 in AD
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.
Dr. Bu's Neurobiology of Alzheimer's Disease Lab is one of the first labs to discover that APOE is a ligand for microglial TREM2, specifically the binding of APOE to TREM2 increases 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.
Dr. Bu's research team collaborates with others to address the pathological role of soluble TREM2 (sTREM) shed from the membrane TREM2 and abundantly present in cerebrospinal fluid and plasma. Further work in the lab seeks to clarify the functional consequence of AD-associated TREM2 variants such as TREM2-R47H, the physiological and pathological roles of sTREM2, and the roles of neuroinflammatory events in general in the neurodegenerative process using biochemical, iPSC-derived myeloid cells, animal models and human specimens.
The TREM2-DAP12 axis modulates homeostatic functions via crosstalk with diverse signaling pathways. Source: Molecular Neurodegeneration. 2015;10:43.