An in situ approach was used to identify the oxidized RNA nucleoside, in the frontal cortex of familial Alzheimer disease (FAD) with a mutation in presenilin-1 (PS-1) or amyloid protein precursor (A PP) gene (n = 13, age 47-81 y). Neurons with marked 8OHG immunoreaction in the cytoplasm were widely distributed in the superior/middle frontal gyrus of FAD. Relative intensity measurements of neuronal 8OHG immunoreactivity showed that there was a significant increase in FAD compared with controls

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... = 15, age 59-81 y), while there was no difference in relative 8OHG between the PS-1 and the A PP FAD. Interestingly, a presymptomatic case carrying a PS-1 mutation showed a considerable level of relative 8OHG, and the increased levels of neuronal 8OHG in FAD were more prominent in cases with lower % area of A 42 burden. These results suggest that oxidative stress is an early event involved in the pathological cascade of FAD.