Amyloid-beta peptides are cytotoxic to oligodendrocytes

Alzheimer's disease (AD) is a neurodegenerative disease characterized by pr ogressive dementia. Amyloid-beta peptide (A beta), a 39-43 amino acid pepti de derived from beta -amyloid precursor protein, forms insoluble fibrillar aggregates that have been linked to neuronal and vascular degeneration in A D and cerebral amyloid angiopathy. Here we demonstrate that A beta 1-40 and a truncated fragment, A beta 25-35, induced death of oligodendrocytes (OLG s) in vitro in a dose-dependent manner with similar potencies. A beta -indu ced OLG death was accompanied by nuclear DNA fragmentation, mitochondrial d ysfunction, and cytoskeletal disintegration. A beta activation of redox-sen sitive transcription factors NF-kappaB and AP-1 and antioxidant prevention of A beta -mediated OLG death suggest that oxidative injury contributes to A beta cytotoxicity in OLGs. Recent demonstration of A beta deposition and white matter abnormalities in AD implies a potential pathophysiological rol e for A beta -mediated cytotoxicity of OLGs in this neurodegenerative disea se.