TREM2 is a receptor for β-amyloid which mediates microglial function

By Yingjun Zhao, Xilin Wu, Xiaoguang Li, Lu-Lin Jiang, X. Gui, Yang Liu, Yu Sun, Bing Zhu, J. Piña-Crespo, Muxian Zhang and 6 more. Neuron, 2018

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SUMMARY Mutations in triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to increased Alzheimer’s disease (AD) risk. Neurobiological functions of TREM2 as well as its pathophysiological ligands remain elusive. Here we found that TREM2 directly binds to β-amyloid (Aβ) oligomers with nanomolar affinity, whereas AD-associated TREM2 mutations reduce Aβ binding. TREM2 deficiency impairs Aβ degradation in primary microglial culture and mouse brain. Aβ-induced microglial depolarization, K+ inward current induction, cytokine expression and secretion, migration, proliferation, apoptosis and morphological changes are dependent on TREM2. In addition, TREM2 interaction with its signaling adaptor DAP12 is enhanced by Aβ, regulating downstream phosphorylation of SYK and GSK3β. Our data demonstrate TREM2 as a microglial Aβ receptor transducing physiological and AD-related pathological effects associated with Aβ.

Subfields: Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/3ce5da781741c2001ecd469a6c5273282db42896