beta-Amyloid-mediated vasoactivity and vascular endothelial damage

Nature. 1996 Mar 14;380(6570):168-71. doi: 10.1038/380168a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / physiology*
  • Animals
  • Aorta
  • Blood Vessels / metabolism
  • Blood Vessels / pathology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / ultrastructure
  • In Vitro Techniques
  • Nerve Degeneration
  • Phenylephrine / pharmacology
  • Rats
  • Superoxides / metabolism*
  • Vasoconstriction
  • Vasoconstrictor Agents / pharmacology
  • Vasodilator Agents / pharmacology


  • Amyloid beta-Peptides
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Superoxides
  • Phenylephrine
  • Acetylcholine