| First Author | Wang Y | Year | 2016 |
| Journal | J Exp Med | Volume | 213 |
| Issue | 5 | Pages | 667-75 |
| PubMed ID | 27091843 | Mgi Jnum | J:233314 |
| Mgi Id | MGI:5781250 | Doi | 10.1084/jem.20151948 |
| Citation | Wang Y, et al. (2016) TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. J Exp Med 213(5):667-75 |
| abstractText | Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial receptor that recognizes changes in the lipid microenvironment, which may occur during amyloid beta (Abeta) accumulation and neuronal degeneration in Alzheimer's disease (AD). Rare TREM2 variants that affect TREM2 function lead to an increased risk of developing AD. In murine models of AD, TREM2 deficiency prevents microglial clustering around Abeta deposits. However, the origin of myeloid cells surrounding amyloid and the impact of TREM2 on Abeta accumulation are a matter of debate. Using parabiosis, we found that amyloid-associated myeloid cells derive from brain-resident microglia rather than from recruitment of peripheral blood monocytes. To determine the impact of TREM2 deficiency on Abeta accumulation, we examined Abeta plaques in the 5XFAD model of AD at the onset of Abeta-related pathology. At this early time point, Abeta accumulation was similar in TREM2-deficient and -sufficient 5XFAD mice. However, in the absence of TREM2, Abeta plaques were not fully enclosed by microglia; they were more diffuse, less dense, and were associated with significantly greater neuritic damage. Thus, TREM2 protects from AD by enabling microglia to surround and alter Abeta plaque structure, thereby limiting neuritic damage. |
