Abstract

Alzheimer’s disease (AD) is the most common form of dementia, which has been currently considered as a genetically complex disorder caused by a combination of environmental and genetic risk factors. Previous studies have reported that triggering receptor expressed on myeloid cells 2 (TREM2) gene represents a promising candidate gene for AD susceptibility and progression. Interestingly, recent findings further suggested that the association between TREM2 variants and AD risk was quite diverse among different ethnicities and populations. As a member of immunoglobulin superfamily, TREM2 protein suppresses inflammatory responses, mediates phagocytic pathways, and contributes to the homeostasis of neuroimmunity in the central nervous system. Emerging evidence has indicated that TREM2 was involved in AD-related neuropathology including amyloid-β deposition, tau hyperphosphorylation, neuroinflammation, and neuronal and synaptic losses in AD animal models, but the precise underlying mechanisms have not been fully characterized yet. Here, we reviewed the new epidemiological findings regarding the association of TREM2 with AD. Meanwhile, we summarized the recent updates about the biological functions of TREM2 and its role in AD pathogenesis. In addition, we also explored the potential TREM2- targeting therapies for AD treatment.

Keywords: Alzheimer’s disease, TREM2, Aβ deposition, tau pathology, microglia, pathogenesis.