Abstract
AbstractAlzheimer’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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference56 articles.
1. Finch, C. E. & Cohen, D. M. Aging, metabolism, and Alzheimer disease: review and hypotheses. Exp. Neurol. 143, 82–102 (1997).
2. Rogers, J. et al. Complement activation by beta-amyloid in Alzheimer disease. Proc. Natl Acad. Sci. USA 89, 10016–10020 (1992).
3. Hensley, K. et al. A model for beta-amyloid aggregation and neurotoxicity based on the free radical generating capacity of the peptide: implications of “molecular shrapnel” for Alzheimer’s disease. Proc. West Pharm. Soc. 38, 113–120 (1995).
4. Heppner, F. L., Ransohoff, R. M. & Becher, B. Immune attack: the role of inflammation in Alzheimer disease. Nat. Rev. Neurosci. 16, 358–372 (2015).
5. von Bernhardi, R. Glial cell dysregulation: a new perspective on Alzheimer disease. Neurotox. Res. 12, 215–232 (2007).
Cited by
24 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献