Amyloid-beta peptides are cytotoxic to oligodendrocytes.
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.
Xu
J
J
Department of Neurology and Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Chen
S
S
Ahmed
S H
SH
Chen
H
H
Ku
G
G
Goldberg
M P
MP
Hsu
C Y
CY
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D018808:Transcription Factor AP-1 / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D016328:NF-kappa B; D010446:Peptide Fragments; D018808:Transcription Factor AP-1; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35)