| First Author | Zhang P | Year | 2019 |
| Journal | Nat Neurosci | Volume | 22 |
| Issue | 5 | Pages | 719-728 |
| PubMed ID | 30936558 | Mgi Jnum | J:281493 |
| Mgi Id | MGI:6378236 | Doi | 10.1038/s41593-019-0372-9 |
| Citation | Zhang P, et al. (2019) Senolytic therapy alleviates Abeta-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer's disease model. Nat Neurosci 22(5):719-728 |
| abstractText | Neuritic plaques, a pathological hallmark in Alzheimer's disease (AD) brains, comprise extracellular aggregates of amyloid-beta (Abeta) peptide and degenerating neurites that accumulate autolysosomes. We found that, in the brains of patients with AD and in AD mouse models, Abeta plaque-associated Olig2- and NG2-expressing oligodendrocyte progenitor cells (OPCs), but not astrocytes, microglia, or oligodendrocytes, exhibit a senescence-like phenotype characterized by the upregulation of p21/CDKN1A, p16/INK4/CDKN2A proteins, and senescence-associated beta-galactosidase activity. Molecular interrogation of the Abeta plaque environment revealed elevated levels of transcripts encoding proteins involved in OPC function, replicative senescence, and inflammation. Direct exposure of cultured OPCs to aggregating Abeta triggered cell senescence. Senolytic treatment of AD mice selectively removed senescent cells from the plaque environment, reduced neuroinflammation, lessened Abeta load, and ameliorated cognitive deficits. Our findings suggest a role for Abeta-induced OPC cell senescence in neuroinflammation and cognitive deficits in AD, and a potential therapeutic benefit of senolytic treatments. |
