Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment

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 F2‐isoprostane (F2‐IsoP) and F4‐neuroprostane (F4‐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 F2‐IsoP and F4‐NP levels. Significant increases in F2‐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 F4‐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 betwen MCI and late AD was significantly increased F4‐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. Ann Neurol 2005;58:730–735