Amyloid-β Peptides Are Cytotoxic to Oligodendrocytes
Open accessAbstract
Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive dementia. Amyloid-beta peptide (Abeta), a 39-43 amino acid peptide derived from beta-amyloid precursor protein, forms insoluble fibrillar aggregates that have been linked to neuronal and vascular degeneration in AD and cerebral amyloid angiopathy. Here we demonstrate that Abeta 1-40 and a truncated fragment, Abeta 25-35, induced death of oligodendrocytes (OLGs) in vitro in a dose-dependent manner with similar potencies. Abeta-induced OLG death was accompanied by nuclear DNA fragmentation, mitochondrial dysfunction, and cytoskeletal disintegration. Abeta activation of redox-sensitive transcription factors NF-kappaB and AP-1 and antioxidant prevention of Abeta-mediated OLG death suggest that oxidative injury contributes to Abeta cytotoxicity in OLGs. Recent demonstration of Abeta deposition and white matter abnormalities in AD implies a potential pathophysiological role for Abeta-mediated cytotoxicity of OLGs in this neurodegenerative disease.
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Exposure of oligodendrocytes to Aβ induces apoptotic cell death.
“The exposure of oligodendrocytes to Aβ induces apoptotic cell death [69]”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [69]
The mitochondrial dysfunction section reports DNA damage and cytochrome c release supportive of apoptosis in Aβ-treated oligodendrocytes. The Discussion says these findings are compatible with apoptosis, but describes the death mechanism as mixed, encompassing both apoptosis and necrosis; the claim presents apoptosis more definitively than the source does. (LLM, conf=0.82)
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- Authors
- Xu, J., Chen, S., Ahmed, S. H., Chen, H., Ku, G., Goldberg, M. P., & Hsu, C. Y.
- Affiliations
- Washington University in St. Louis (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-01-01
- Volume
- 21
- Issue
- 1
- Pages
- RC118-RC118
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762453
- OpenAlex
- W1492053682
- Cited by
- 230
- References
- 3
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 7 · 2023: 19 · 2022: 4 · 2021: 8 · 2020: 10 · 2019: 9 · 2018: 11 · 2017: 5 · 2016: 10 · 2015: 12 · 2014: 9 · 2013: 8 · 2012: 7
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29ns032140-05, 5r01ns025545-10, 5r01ns028995-10)
- Office of Naval Research
- National Institute of Neurological Disorders and Stroke (NS-25545, NS32140, NS 28995)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta, oligodendrocytes, cytotoxicity, Alzheimer's disease, Aβ(1-40), amyloid beta 25-35, oxidative stress, mitochondrial dysfunction, DNA fragmentation, NF-κB, AP-1, white matter abnormalities, cerebral amyloid angiopathy
- MeSH terms
- Alzheimer Disease, Animals, Antioxidants, Cells, Cultured, Cytoskeleton, Dose-Response Relationship, Drug, Mitochondria, Oligodendroglia, Peptide Fragments, Amyloid beta-Peptides, NF-kappa B, Oxidative Stress, Transcription Factor AP-1, Rats, DNA Fragmentation
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