beta-Amyloid (Abeta) is considered to be responsible for the formation of senile plaques that accumulate in the brains of patients with Alzheimer's disease (AD). There is compelling evidence supporting the notion that Abeta-induced cytotoxicity is mediated through the generation of reactive oxygen species (ROS). Recently, considerable attention has been focused on a wide array of non-vitamin antioxidants present in edible plants that are able to scavenge ROS, thereby protecting against oxidative damage. In this study, we have investigated the possible protective effects of formulated polyphenol oligomers (Oligonol) derived from grape seed extracts on Abeta-induced oxidative cell death. Rat pheochromocytoma (PC12) cells treated with Abeta exhibited increased accumulation of intracellular ROS and underwent apoptosis, as determined by positive in situ terminal end labeling, decreased mitochondrial membrane potential, and the cleavage of poly(ADP-ribose)polymerase. Oligonal attenuated Abeta-induced cytotoxicity, apoptotic features, intracellular ROS accumulation, and lipid peroxidation and increased the cellular glutathione pool. Moreover, Abeta transiently induced the activation of nuclear factor kappaB in PC12 cells, which was suppressed by pretreatment with Oligonol.