Vitamin E protects against Alzheimer's amyloid peptide (25-35)-induced changes in neocortical synaptosomal membrane lipid structure and composition.

Ž . Alzheimer’s disease AD is an age-related, neurodegenerative disorder characterized by the presence of brainŽ . resident neurofibrillary tangles, senile plaques SP , and w x loss of synapses 9 . The major component of SP is the Ž . aggregated form of amyloid b-peptide A b , which is w x 39–43 amino acids in length 19 . A b is associated with free radical oxidative stress as demonstrated in many laboratories, including our own, employing electron paraŽ . magnetic resonance EPR spin trapping and spin labeling, measuring A b-induced protein and lipid oxidation, and investigating effects of A b on oxidation of and dysfunctions in proteins of brain membranes and neuronal cultures w x and their prevention by free radical antioxidants 2,6,7 . We proposed that A b-associated free radical lipid peroxidation and the peroxidation product 4-hydroxynonenal Ž . HNE may be related to the primary mechanism for brain w x cell death in AD 7,20 . The purpose of the current study was to assess further Ž . the damage caused by A b 25–35 , specifically to the lipid domain of cortical synaptosomal membranes using Ž EPR and the lipid-specific spin label 12-NS 12-nitroxyl . w x Ž . stearate 3 and measuring free fatty acids FFA , a marker w x of lipid peroxidation 4 . If A b-induced lipid peroxidation is indeed free radical mediated then, a lipid-soluble free radical scavenger like vitamin E is predicted to protect against such damage.