MELATONIN PREVENTS BETA-AMYLOID-INDUCED LIPID-PEROXIDATION

beta-Amyloid is a major constituent of senile plaques that occur in th e brains of Alzheimer's disease (AD) patients. Cell culture studies ha ve shown that high concentrations of beta-amyloid are toxic and damage biological macromolecules. A number of experiments have shown that me latonin is a potent antioxidant. Melatonin not only neutralizes oxygen -derived free radicals but can also scavenge species of other types su ch as carbon-centered free radicals. The present study was designed to determine whether beta-amyloid toxicity would cause lipid peroxidatio n of human platelet membranes. Since aluminum has been implicated in t he etiology of AD, we investigated the effects of aluminum on lipid pe roxidation and whether the harmful effects of beta-amyloid are aggrava ted by aluminum. We also investigated whether melatonin had the abilit y to protect against beta-amyloid toxicity. Our results indicate that both beta-amyloid and aluminum dose-dependently increased lipid peroxi dation in platelet membranes. Aluminum was more potent than beta-amylo id. Incubation of platelet membranes with increasing concentrations of aluminum in the presence of 100 mu M beta-amyloid (fragment 25-35) re sulted in lipid peroxidation levels of similar magnitude as the two su bstances, respectively. Prior administration of melatonin dose-depende ntly inhibited this effect. These results confirm the toxic effects of beta-amyloid to biological membranes. While aluminum itself damages m embranes, its presence did not exacerbate the toxic effects of beta-am yloid. Melatonin effectively reduced the lipid peroxidation induced by beta-amyloid and aluminum, suggesting that its supplementation to AD patients may be beneficial.