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Letters to Nature
Nature 380, 168 - 171 (14 March 1996); doi:10.1038/380168a0

β-Amyloid-mediated vasoactivity and vascular endothelial damage

Tom Thomas, George Thomas*, Chris McLendon, Truitt Sutton & Michael Mullan

*Roskamp Laboratories, Institute for Research in Psychiatry, and Department of Physiology and Biophysics, College of Medicine, University of South Florida, Tampa, Florida 33613, USA
* Present address: Nitromed, Research Laboratories, Cambridge, Massachusetts, USA.

DEPOSITS of β-amyloid are apparent in ageing and Alzheimer's disease1, but the role of this peptide in neurodegeneration is unclear2. The free-radical theory of ageing may also account for Alzheimer-type degeneration and consequently links between free-radical generation and β-amyloid have been sought3. We demonstrate here that β-amyloid interacts with endothelial cells on blood vessels to produce an 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 changes4. 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 β-amyloid as well as a mechanism by which β-amyloid may play a role in vascular abnormalities and neurodegeneration mediated by free radicals.

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