The role of TREM2 in Alzheimer's disease: from the perspective of Tau

Front Cell Dev Biol. 2023 Nov 8:11:1280257. doi: 10.3389/fcell.2023.1280257. eCollection 2023.

Abstract

Triggering receptor expressed on myeloid cells 2 (TREM2), a pattern recognition receptor abundantly expressed on microglia, has been identified as one of the risk factors for Alzheimer's disease (AD). Several studies have already demonstrated the relationship between TREM2 and Tau. TREM2 mutations and altered expression play an important role in Tau phosphorylation. Furthermore, the level of Tau phosphorylation is correlated with soluble TREM2 (sTREM2). However, in different stages of AD, TREM2 seems to have varying effects on Tau pathology. The explicit interaction between TREM2 and Tau, as well as how they affect AD pathology, remains unclear, and there is much evidence to the contrary that requires rational interpretation. Reviewing the dual roles of TREM2 in AD will help identify a more appropriate development strategy for targeting TREM2 to treat AD. Therefore, this review focuses on the interplay between Tau and TREM2 in relation to AD.

Keywords: Alzheimer’s disease; Tau; Tau pathology; microglia; neuroinflammation; phosphorylation; soluble TREM2; triggering receptor expressed on myeloid cells 2.

Publication types

  • Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (82160858), Science and Technology Department of Guizhou Province (ZK (2021)-570), Zunyi Science and Technology Bureau (HZ-2022-45), and Funds of The First People’s Hospital of Zunyi for Research and Experimental Development (R&D 2020-06).