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

"beta Amyloid (A beta)-induced free radical-mediated neurotoxicity" is a le ading hypothesis as a cause of Alzheimer's disease (AD). A beta increased f ree radical production and lipid peroxidation in PC12 nerve cells, leading to increased 3-hydroxy-2-nonenal (HNE) production and modification of speci fic mitochondrial target proteins, apoptosis and cell death. Pretreatment o f the cells with isolated ginkgolides, the anti-oxidant component of Ginkgo biloba leaves, or vitamin E, prevented the A beta-induced increase of reac tive oxygen species (ROS). Ginkgolides, but not vitamin E, inhibited the A beta-induced HNE modification of mitochondrial proteins. However, treatment with these anti-oxidants did not rescue the cells from A beta-induced apop tosis and cell death. These results indicate that free radicals and Lipid p eroxidation may not mediate A beta-induced neurotoxicity. (C) 1999 Elsevier Science B.V. All rights reserved.