Multiple studies demonstrate that the brain in Alzheimer's disease (AD) contains extensive oxidative damage. Most of these studies used advanced-stage AD patients raising the question of whether oxidative damage is a late effect of neurodegeneration or precedes and contributes to the pathogenesis of AD. Here we describe F(2)-isoprostane (F(2)-IsoP) and F(4)-neuroprostane (F(4)-NP) levels in longitudinally followed, well documented autopsied normal control subjects and patients with amnestic mild cognitive impairment (MCI), and late-stage AD. Gas chromatography/negative ion chemical ionization/mass spectrometry was used to determine F(2)-IsoP and F(4)-NP levels. Significant increases in F(2)-IsoP levels were found in frontal, parietal and occipital lobes in MCI and late AD compared to controls but no significant differences were present between MCI and late AD. A significant increase in F(4)-NPs was present in parietal and occipital lobes in MCI compared to controls and a significant increase was present in these regions and hippocampus in late AD compared to controls. The only difference between MCI and late AD was significantly increased F(4)-NP in hippocampus in late AD. Our data indicate that lipid peroxidation is present in the brain of MCI patients and suggest that oxidative damage may play a role in the pathogenesis of AD.