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

'β Amyloid (Aβ)-induced free radical-mediated neurotoxicity' is a leading hypothesis as a cause of Alzheimer's disease (AD). Aβ 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 Aβ-induced increase of reactive oxygen species (ROS). Ginkgolides, but not vitamin E, inhibited the Aβ-induced HNE modification of mitochondrial proteins. However, treatment with these anti- oxidants did not rescue the cells from Aβ-induced apoptosis and cell death. These results indicate that free radicals and lipid peroxidation may not mediate Aβ-induced neurotoxicity.