beta-Amyloid-mediated vasoactivity and vascular endothelial damage.
Deposits of beta-amyloid are apparent in ageing and Alzheimer's disease, but the role of this peptide in neurodegeneration is unclear. The free-radical theory of ageing may also account for Alzheimer-type degeneration and consequently links between free-radical generation and beta-amyloid have been sought. We demonstrate here that beta-amyloid interacts with endothelial cells on blood vessels to produce and excess of superoxide radicals, with attendant alterations in endothelial structure and function. The superoxide radical can scavenge endothelium-derived relaxing factor and produce potent oxidizing agents, which can cause lipid peroxidation and other degenerative changes. The alterations in vascular tone and endothelial damage are prevented by the oxygen-radical-scavenging enzyme superoxide dismutase. These observations suggest a normal vasoactive role for beta-amyloid as well as a mechanism by which beta-amyloid may play a role in vascular abnormalities and neurodegeneration mediated by free radicals.
Thomas
T
T
Roskamp Laboratories, Institute for Research in Psychiatry, University of South Florida, Tampa, 33613 USA.
Thomas
G
G
McLendon
C
C
Sutton
T
T
Mullan
M
M
D000109:Acetylcholine / Q000494:pharmacology; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D001011:Aorta; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D009410:Nerve Degeneration; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D013481:Superoxides / Q000378:metabolism*; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D013481:Superoxides; D010656:Phenylephrine; D000109:Acetylcholine