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

Hanseul Park, Byounggook Cho, Hongwon Kim, Takashi Saito, Takaomi C. Saido, Kyoung-Jae Won () and Jongpil Kim ()
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Hanseul Park: Dongguk University
Byounggook Cho: Dongguk University
Hongwon Kim: Dongguk University
Takashi Saito: RIKEN Center for Brain Science
Takaomi C. Saido: RIKEN Center for Brain Science
Kyoung-Jae Won: Cedars-Sinai Medical Center 700 N
Jongpil Kim: Dongguk University

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Alzheimer’s disease (AD) is associated with progressive neuronal degeneration as amyloid-beta (Aβ) 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 AppNL-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 AppNL-G-F mouse brains. Notably, inhibition of Erk1/2 signaling in DAOs rescued impaired axonal myelination and ameliorated Aβ-associated pathologies and cognitive decline in the male AppNL-G-F AD mouse model.

Date: 2023
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DOI: 10.1038/s41467-023-36519-8

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