EVIDENCE FOR NEURONAL OXIDATIVE DAMAGE IN ALZHEIMERS-DISEASE

Oxidative stress has been proposed as a pathogenetic mechanism in Alzh eimer's disease. One mechanism of oxidative damage is the nitration of tyrosine residues in proteins, mediated by peroxynitrite breakdown. P eroxynitrite, a reaction product of nitric oxide and superoxide radica ls, has been implicated in N-methyl-D-aspartate receptor-mediated exci totoxic damage. Reported evidence of oxidative stress in Alzheimer's d isease includes increased iron, alterations in protective enzymes, and markers of oxidative damage to proteins and lipids. In this report, w e demonstrate the presence of nitrotyrosine in neurofibrillary tangles of Alzheimer's disease. nitrotyrosine was not detected in controls la cking neurofibrillary tangles. Immunolabeling was demonstrated to be s pecific for nitrotyrosine in a series of control experiments. These ob servations link oxidative stress with a key pathological lesion of Alz heimer's disease, the neurofibrillary tangle, and demonstrate a pathog enetic mechanism in common with the other major neurodegenerative dise ases of aging, Parkinson's disease and amyotrophic lateral sclerosis. These findings further implicate nitric oxide expression and excitotox icity in the pathogenesis of cell death in Alzheimer's disease.