| First Author | Zhao Y | Year | 2018 |
| Journal | Neuron | Volume | 97 |
| Issue | 5 | Pages | 1023-1031.e7 |
| PubMed ID | 29518356 | Mgi Jnum | J:260524 |
| Mgi Id | MGI:6150565 | Doi | 10.1016/j.neuron.2018.01.031 |
| Citation | Zhao Y, et al. (2018) TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function. Neuron 97(5):1023-1031.e7 |
| abstractText | Mutations in triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to increased Alzheimer''s disease (AD) risk. Neurobiological functions of TREM2 and its pathophysiological ligands remain elusive. Here we found that TREM2 directly binds to beta-amyloid (Abeta) oligomers with nanomolar affinity, whereas AD-associated TREM2 mutations reduce Abeta binding. TREM2 deficiency impairs Abeta degradation in primary microglial culture and mouse brain. Abeta-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 Abeta, regulating downstream phosphorylation of SYK and GSK3beta. Our data demonstrate TREM2 as a microglial Abeta receptor transducing physiological and AD-related pathological effects associated with Abeta. |
