Amyloid-beta peptides are cytotoxic to oligodendrocytes

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive dementia. Amyloid-beta peptide (A beta), 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 A beta 1-40 and a truncated fragment, A beta 25-35, induced death of oligodendrocytes (OLGs) in vitro in a dose-dependent manner with similar potencies. A beta -induced OLG death was accompanied by nuclear DNA fragmentation, mitochondrial dysfunction, and cytoskeletal disintegration. A beta activation of redox-sensitive 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 role for A beta -mediated cytotoxicity of OLGs in this neurodegenerative disease.