Brain Sciences, Vol. 13, Pages 642: The TREM2 H157Y Variant Influences Microglial Phagocytosis, Polarization, and Inflammatory Cytokine Release

Brain Sciences, Vol. 13, Pages 642: The TREM2 H157Y Variant Influences Microglial Phagocytosis, Polarization, and Inflammatory Cytokine Release

Brain Sciences doi: 10.3390/brainsci13040642

Authors: Xin-Xin Fu Shuai-Yu Chen Hui-Wen Lian Yang Deng Rui Duan Ying-Dong Zhang Teng Jiang

Previously, we reported that H157Y, a rare coding variant on exon 3 of the triggering receptor expressed on myeloid cells 2 gene (TREM2), was associated with Alzheimer’s disease (AD) risk in a Han Chinese population. To date, how this variant increases AD risk has remained unclear. In this study, using CRISPR-Cas9-engineered BV2 microglia, we tried to investigate the influence of the Trem2 H157Y variant on AD-related microglial functions. For the first time, we revealed that the Trem2 H157Y variant inhibits microglial phagocytosis of amyloid-β, promotes M1-type polarization of microglia, and facilitates microglial release of inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. These findings provide new insights into the cellular mechanisms by which the TREM2 H157Y variant elevates the risk of AD.