| First Author | Lee SH | Year | 2021 |
| Journal | Neuron | Volume | 109 |
| Issue | 8 | Pages | 1283-1301.e6 |
| PubMed ID | 33675684 | Mgi Jnum | J:304468 |
| Mgi Id | MGI:6690326 | Doi | 10.1016/j.neuron.2021.02.010 |
| Citation | Lee SH, et al. (2021) Trem2 restrains the enhancement of tau accumulation and neurodegeneration by beta-amyloid pathology. Neuron |
| abstractText | Loss-of-function TREM2 mutations strongly increase Alzheimer's disease (AD) risk. Trem2 deletion has revealed protective Trem2 functions in preclinical models of beta-amyloidosis, a prominent feature of pre-diagnosis AD stages. How TREM2 influences later AD stages characterized by tau-mediated neurodegeneration is unclear. To understand Trem2 function in the context of both beta-amyloid and tau pathologies, we examined Trem2 deficiency in the pR5-183 mouse model expressing mutant tau alone or in TauPS2APP mice, in which beta-amyloid pathology exacerbates tau pathology and neurodegeneration. Single-cell RNA sequencing in these models revealed robust disease-associated microglia (DAM) activation in TauPS2APP mice that was amyloid-dependent and Trem2-dependent. In the presence of beta-amyloid pathology, Trem2 deletion further exacerbated tau accumulation and spreading and promoted brain atrophy. Without beta-amyloid pathology, Trem2 deletion did not affect these processes. Therefore, TREM2 may slow AD progression and reduce tau-driven neurodegeneration by restricting the degree to which beta-amyloid facilitates the spreading of pathogenic tau. |
