Does human betaA4 exert a protective function against oxidative stress in Alzheimer's disease?

The hypothesis is advanced that human betaA4--as opposed to rodent betaA4--may exert a protective function against the iron-induced oxidative stress associated with neurological diseases (notably Alzheimer's disease). Subsequent to its release by the host in response to oxidative injury, human betaA4 would interact with Cu(2+)ions whose level is correlatively elevated, adopting the 'aggregated' structure recently characterized by Atwood et al.(15). Then, depending on the oxidative state--hence the pH--of the medium, it might either return to its original structure if physiological pH is restored, or undergo site-specific copper-mediated oxidation and, finally, degradation. In this context, betaA4 pathogenicity could be due to an interfering mechanism preventing the degradation of the oxidized peptide, making its aggregation irreversible and inducing its final deposition. Coordination of side group oxygen donors of the oxidized peptide with 'hard' metal ions occurring in the physiological medium (notably Al(3+)) might be at the origin of this interference.