Review: Alzheimer's amyloid beta-peptide-associated free radical oxidativestress and neurotoxicity

Alzheimer's disease, the major dementing disorder of the elderly that affec ts over 4 million Americans, is related to amyloid beta-peptide, the princi pal component of senile plaques in Alzheimer's disease brain. Oxidative str ess, manifested by protein oxidation and lipid peroxidation, among other al terations, is a characteristic of Alzheimer's disease brain. Our laboratory united these two observations in a model to account for neurodegeneration in Alzheimer's disease brain, the amyloid beta-peptide-associated oxidative stress model for neurotoxicity in Alzheimer's disease. Under this model, t he aggregated peptide, perhaps in concert with bound redox metal ions, init iates free radical processes resulting in protein oxidation, lipid peroxida tion, reactive oxygen species formation, cellular dysfunction leading to ca lcium ion accumulation, and subsequent neuronal death. Free radical antioxi dants abrogate these findings. This review outlines the substantial evidenc e from multiidisciplinary approaches for amyloid beta-peptide-associated fr ee radical oxidative stress and neurotoxicity and protection against these oxidative processes and cell death by free radical scavengers. In addition, we review the strong evidence supporting the notion that the single methio nine residue of amyloid beta-peptide is vital to the oxidative stress and n eurotoxicological properties of this peptide. Further, we discuss studies t hat support the hypothesis that aggregated soluble amyloid beta-peptide and not fibrils per se are necessary for oxidative stress and neurotoxicity as sociated with amyloid beta-peptide. (C) 2000 Academic Press.