| First Author | Safaiyan S | Year | 2021 |
| Journal | Neuron | Volume | 109 |
| Issue | 7 | Pages | 1100-1117.e10 |
| PubMed ID | 33606969 | Mgi Jnum | J:306947 |
| Mgi Id | MGI:6706971 | Doi | 10.1016/j.neuron.2021.01.027 |
| Citation | Safaiyan S, et al. (2021) White matter aging drives microglial diversity. Neuron 109(7):1100-1117.e10 |
| abstractText | Aging results in gray and white matter degeneration, but the specific microglial responses are unknown. Using single-cell RNA sequencing from white and gray matter separately, we identified white matter-associated microglia (WAMs), which share parts of the disease-associated microglia (DAM) gene signature and are characterized by activation of genes implicated in phagocytic activity and lipid metabolism. WAMs depend on triggering receptor expressed on myeloid cells 2 (TREM2) signaling and are aging dependent. In the aged brain, WAMs form independent of apolipoprotein E (APOE), in contrast to mouse models of Alzheimer's disease, in which microglia with the WAM gene signature are generated prematurely and in an APOE-dependent pathway similar to DAMs. Within the white matter, microglia frequently cluster in nodules, where they are engaged in clearing degenerated myelin. Thus, WAMs may represent a potentially protective response required to clear degenerated myelin accumulating during white matter aging and disease. |
