Vitamin E prevents Alzheimer's amyloid β-peptide (1-42)-induced neuronal protein oxidation and reactive oxygen species production

Amyloid β-peptide (Aβ) is a 42-43 amino acid peptide known to accumulate in Alzheimer's disease (AD) brain. We previously reported that the neurotoxicity caused by Aβ is a result of its associated free radicals, which can play an important role in generating oxidative stress. Aβ(25-35)-associated oxidative stress-induced neuronal death in vitro is well established by many laboratories, including ours. However, the oxidative stress-induced by the full-length [Aβ(1-42)] peptide is not well investigated. The protective effect of antioxidant vitamin E in full-length peptide-induced oxidative stress also has not been reported. Here, we report, that the increased protein oxidation, reactive oxygen species (ROS) formation, and neurotoxicity indUced by Aβ(1-42) in primary rat embryonic hippocampal neuronal culture are prevented by the free radical scavenger and anti-oxidant vitamin E. To test the hypothesis that vitamin E's protective effect may be due to inhibition, of fibril formation, electron microscopy studies were undertaken. Vitamin E does not inhibit Aβ(1-42) fibril formation, suggesting that the neuroprotection afforded by this molecule stems from other processes, most probably through the scavenging of Aβ-associated free radicals. These results may have implications on the treatment of Alzheimer's disease.