| First Author | Hu Y | Year | 2021 |
| Journal | Cell Rep | Volume | 35 |
| Issue | 10 | Pages | 109228 |
| PubMed ID | 34107254 | Mgi Jnum | J:311267 |
| Mgi Id | MGI:6717003 | Doi | 10.1016/j.celrep.2021.109228 |
| Citation | Hu Y, et al. (2021) Replicative senescence dictates the emergence of disease-associated microglia and contributes to Abeta pathology. Cell Rep 35(10):109228 |
| abstractText | The sustained proliferation of microglia is a key hallmark of Alzheimer's disease (AD), accelerating its progression. Here, we aim to understand the long-term impact of the early and prolonged microglial proliferation observed in AD, hypothesizing that extensive and repeated cycling would engender a distinct transcriptional and phenotypic trajectory. We show that the early and sustained microglial proliferation seen in an AD-like model promotes replicative senescence, characterized by increased betagal activity, a senescence-associated transcriptional signature, and telomere shortening, correlating with the appearance of disease-associated microglia (DAM) and senescent microglial profiles in human post-mortem AD cases. The prevention of early microglial proliferation hinders the development of senescence and DAM, impairing the accumulation of Abeta, as well as associated neuritic and synaptic damage. Overall, our results indicate that excessive microglial proliferation leads to the generation of senescent DAM, which contributes to early Abeta pathology in AD. |
