Increased Nuclear DNA Oxidation in the Brain in Alzheimer's Disease

摘要: Multiple lines of evidence indicate that oxidative stress is a contributor to neuronal death in Alzheimer's disease (AD). The damage occurs DNA may play role both normal aging and neurodegenerative diseases, including AD. This study the nuclear brains AD patients cognitively intact, prospectively evaluated, age-matched control subjects. Nuclear from frontal, temporal, parietal lobes cerebellum was isolated 11 subjects 9 subjects, oxidized purine pyrimidine bases were quantitated using gas chromatography/mass spectrometry. Stable isotope-labeled base analogues used as internal standards measure 5-hydroxyuracil, 5-hydroxycytosine, 8-hydroxyadenine, 4,6-diamino-5-formamidopyrimidine (Fapy-adenine), 8-hydroxyguanine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy-guanine). Statistically significant elevations 8-hydroxyguanine found brain compared with (p < 0.05). There an increased trend levels Fapy-adenine brain, Fapy-guanine showed toward higher A generally level present neocortical regions than cerebellum. No correlation observed between neurofibrillary tangle senile plaque counts. Our results demonstrate by oxygen-derived radicals support concept under