Neuronal RNA oxidation is a prominent feature of familial Alzheimer's disease

An in situ approach was used to identify the oxidized RNA nucleoside 8-hydroxyguanosine (8OHG) in the frontal cortex of familial Alzheimer's disease (FAD) with a mutation in presenilin-1 (PS-1) or amyloid protein precursor (AOPP) gene (n = 13, age 47-81 years). Neurons with marked 80HG immunoreaction in the cytoplasm were widely distributed in the superior/middle frontal gyros of FAD. Relative intensity measurements of neuronal 80HG immunoreactivity showed that there was a significant increase in FAD compared with controls (n = 15, age 59-81 years), while there was no difference in relative 80HG between the PS-1 and the AOPP FAD. Interestingly, a presymptomatic case carrying a PS-1 mutation showed a considerable level of relative 8OHG, and the increased levels of neuronal 80HG in FAD were more prominent in cases with a lower percentage area of Abeta42 burden. These results suggest that oxidative stress is an early event involved in the pathological cascade of FAD. (C) 2004 Elsevier Inc. All rights reserved.