AN ASSESSMENT OF OXIDATIVE DAMAGE TO PROTEINS, LIPIDS, AND DNA IN BRAIN FROM PATIENTS WITH ALZHEIMERS-DISEASE

Oxidative stress may contribute to neuronal loss in Alzheimer's diseas e (AD). The present study compares the levels of oxidative damage to p roteins, lipids, and DNA bases from seven different brain areas of AD and matched control tissues by using a range of techniques. No differe nces in levels of lipid peroxidation were found in any of the brain re gions by using two different assay systems. Overall, there was a trend for protein carbonyl levels to be increased in AD in frontal, occipit al, parietal, and temporal lobe, middle temporal gyrus, and hippocampu s, but a significant difference was found only in the parietal robe. G as chromatography-mass spectrometry was used to measure products of da mage to all four DNA bases. Increased levels of some (8-hydroxyadenine , 8-hydroxyguanine, thymine glycol, Fapy-guanine, 5-hydroxyuracil, and Fapy-adenine), but not all, oxidized DNA bases were observed in parie tal, temporal, occipital, and frontal lobe, superior temporal gyrus, a nd hippocampus. The baseline level of oxidative DNA damage in the temp oral lobe was higher than in other brain regions in both control and A D brain. The finding of increased oxidative damage to protein and DNA strengthens the possibility that oxidative damage may play a role in t he pathogenesis of AD in at least some key brain regions.