%0 Journal Article
%T Senolytic therapy alleviates A¦Â-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer¡¯s disease model
%J -
%D 2019
%R https://doi.org/10.1038/s41593-019-0372-9
%X Neuritic plaques, a pathological hallmark in Alzheimer¡¯s disease (AD) brains, comprise extracellular aggregates of amyloid-beta (A¦Â) peptide and degenerating neurites that accumulate autolysosomes. We found that, in the brains of patients with AD and in AD mouse models, A¦Â 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 ¦Â-galactosidase activity. Molecular interrogation of the A¦Â plaque environment revealed elevated levels of transcripts encoding proteins involved in OPC function, replicative senescence, and inflammation. Direct exposure of cultured OPCs to aggregating A¦Â triggered cell senescence. Senolytic treatment of AD mice selectively removed senescent cells from the plaque environment, reduced neuroinflammation, lessened A¦Â load, and ameliorated cognitive deficits. Our findings suggest a role for A¦Â-induced OPC cell senescence in neuroinflammation and cognitive deficits in AD, and a potential therapeutic benefit of senolytic treatments
%U https://www.nature.com/articles/s41593-019-0372-9