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.
|Original language||English (US)|
|Journal||The Journal of neuroscience : the official journal of the Society for Neuroscience|
|State||Published - Jan 1 2001|
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