Amyloid beta-peptide (Abeta), the major constituent in senile plaques in Alzheimer's disease (AD) brain, is thought by many researchers to be central to neurotoxicity in AD brain. Increasing evidence from many laboratories indicates that AD brain is under oxidative stress, with strong evidence of protein oxidation, lipid peroxidation, and peroxynitrite damage. A link between the central role of Abeta and oxidative stress in AD brain may be Abeta-associated free radical oxidative stress. If so, antioxidants such as vitamin E should modulate Abeta-induced oxidative damage and neurotoxicity in brain cells. This review summarizes studies of Abeta-associated free radical oxidative stress and its inhibition by vitamin E in cortical synaptosomal membranes and hippocampal neuronal cells in culture. Taken together with the recent report that vitamin E slows the progression of AD, this review strongly supports a central role of Abeta-associated free radical oxidative stress in neurotoxicity in AD brain.