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Publication : Single-cell RNA-sequencing identifies disease-associated oligodendrocytes in male APP NL-G-F and 5XFAD mice.

First Author  Park H Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  802
PubMed ID  36781874 Mgi Jnum  J:341266
Mgi Id  MGI:7438072 Doi  10.1038/s41467-023-36519-8
Citation  Park H, et al. (2023) Single-cell RNA-sequencing identifies disease-associated oligodendrocytes in male APP NL-G-F and 5XFAD mice. Nat Commun 14(1):802
abstractText  Alzheimer's disease (AD) is associated with progressive neuronal degeneration as amyloid-beta (Abeta) and tau proteins accumulate in the brain. Glial cells were recently reported to play an important role in the development of AD. However, little is known about the role of oligodendrocytes in AD pathogenesis. Here, we describe a disease-associated subpopulation of oligodendrocytes that is present during progression of AD-like pathology in the male App(NL-G-F) and male 5xFAD AD mouse brains and in postmortem AD human brains using single-cell RNA sequencing analysis. Aberrant Erk1/2 signaling was found to be associated with the activation of disease-associated oligodendrocytes (DAOs) in male App(NL-G-F) mouse brains. Notably, inhibition of Erk1/2 signaling in DAOs rescued impaired axonal myelination and ameliorated Abeta-associated pathologies and cognitive decline in the male App(NL-G-F) AD mouse model.
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