Oxidative Damage Is Associated with the Onset of Cognitive Impairment in Very Mild Alzheimer's Disease

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An in situ approach was used to identify an oxidized nucleoside, 8-hydroxyguanosine in the cerebral cortex of postmortem brains. Density measurements of the immunoreactions revealed a modest but statistically significant increase in neuronal RNA oxidation during aging (0.3 to 86 years old). In the subjects with very mild Alzheimer's disease (AD), but not preclinical AD, neurons showed higher burden of oxidized RNA compared to age-matched controls. Prominent levels of neuronal RNA oxidation are associated with the earliest changes marking the onset of cognitive impairment in the prodromal stage of AD.