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

Abstract

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 β protein precursor (AβPP) gene ( n = 13, age 47–81 years). 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 ( n = 15, age 59–81 years), while there was no difference in relative 8OHG between the PS-1 and the AβPP 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 a lower percentage area of Aβ42 burden. These results suggest that oxidative stress is an early event involved in the pathological cascade of FAD.