Free radicals and lipid peroxidation do not mediate beta-amyloid-induced neuronal cell death

"beta Amyloid (Abeta)-induced free radical-mediated neurotoxicity" is a leading hypothesis as a cause of Alzheimer's disease (AD). Abeta increased free radical production and lipid peroxidation in PC12 nerve cells, leading to increased 4-hydroxy-2-nonenal (HNE) production and modification of specific mitochondrial target proteins, apoptosis and cell death. Pretreatment of the cells with isolated ginkgolides, the anti-oxidant component of Ginkgo biloba leaves, or vitamin E, prevented the Abeta-induced increase of reactive oxygen species (ROS). Ginkgolides, but not vitamin E, inhibited the Abeta-induced HNE modification of mitochondrial proteins. However, treatment with these anti-oxidants did not rescue the cells from Abeta-induced apoptosis and cell death. These results indicate that free radicals and lipid peroxidation may not mediate Abeta-induced neurotoxicity.