| First Author | Leyns CEG | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 43 | Pages | 11524-11529 |
| PubMed ID | 29073081 | Mgi Jnum | J:256924 |
| Mgi Id | MGI:6095556 | Doi | 10.1073/pnas.1710311114 |
| Citation | Leyns CEG, et al. (2017) TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy. Proc Natl Acad Sci U S A 114(43):11524-11529 |
| abstractText | Variants in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) were recently found to increase the risk for developing Alzheimer's disease (AD). In the brain, TREM2 is predominately expressed on microglia, and its association with AD adds to increasing evidence implicating a role for the innate immune system in AD initiation and progression. Thus far, studies have found TREM2 is protective in the response to amyloid pathology while variants leading to a loss of TREM2 function impair microglial signaling and are deleterious. However, the potential role of TREM2 in the context of tau pathology has not yet been characterized. In this study, we crossed Trem2(+/+) (T2(+/+)) and Trem2(-/-) (T2(-/-)) mice to the PS19 human tau transgenic line (PS) to investigate whether loss of TREM2 function affected tau pathology, the microglial response to tau pathology, or neurodegeneration. Strikingly, by 9 mo of age, T2(-/-)PS mice exhibited significantly less brain atrophy as quantified by ventricular enlargement and preserved cortical volume in the entorhinal and piriform regions compared with T2(+/+)PS mice. However, no TREM2-dependent differences were observed for phosphorylated tau staining or insoluble tau levels. Rather, T2(-/-)PS mice exhibited significantly reduced microgliosis in the hippocampus and piriform cortex compared with T2(+/+)PS mice. Gene expression analyses and immunostaining revealed microglial activation was significantly attenuated in T2(-/-)PS mice, and there were lower levels of inflammatory cytokines and astrogliosis. These unexpected findings suggest that impairing microglial TREM2 signaling reduces neuroinflammation and is protective against neurodegeneration in the setting of pure tauopathy. |
