Triggering Receptor Expressed on Myeloid Cells 2 (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 (sTREM2) 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.

Key Publications

Atagi Y, Liu CC, Painter MM, Chen XF, Verbeeck C, Zheng H, Li X, Rademakers R, Kang SS, Xu H, Younkin S, Das P, Fryer JD, Bu G. Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). Journal of Biological Chemistry. 2015; doi:10.1074/jbc.M115.679043

Painter MM, Atagi Y, Liu CC, Rademakers R, Xu H, Fryer JD, Bu G. TREM2 in CNS homeostasis and neurodegenerative disease. Molecular Neurodegeneration. 2015; doi:10.1186/s13024-015-0040-9