title: An assessment of oxidative damage to proteins, lipids, and DNA in brain from patients with Alzheimer's disease.
abstract: Oxidative stress may contribute to neuronal loss in Alzheimer's disease (AD). The present study compares the levels of oxidative damage to proteins, lipids, and DNA bases from seven different brain areas of AD and matched control tissues by using a range of techniques. No differences in levels of lipid peroxidation were found in any of the brain regions by using two different assay systems. Overall, there was a trend for protein carbonyl levels to be increased in AD in frontal, occipital, parietal, and temporal lobe, middle temporal gyrus, and hippocampus, but a significant difference was found only in the parietal lobe. Gas chromatography-mass spectrometry was used to measure products of damage 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 parietal, temporal, occipital, and frontal lobe, superior temporal gyrus, and hippocampus. The baseline level of oxidative DNA damage in the temporal lobe was higher than in other brain regions in both control and AD brain. The finding of increased oxidative damage to protein and DNA strengthens the possibility that oxidative damage may play a role in the pathogenesis of AD in at least some key brain regions.
authors.affiliation: Neurodegenerative Disease Research Centre, Pharmacology Group, King's College, London, England.
authors.forename: L
authors.initials: L
authors.lastname: Lyras
authors.forename: N J
authors.initials: NJ
authors.lastname: Cairns
authors.forename: A
authors.initials: A
authors.lastname: Jenner
authors.forename: P
authors.initials: P
authors.lastname: Jenner
authors.forename: B
authors.initials: B
authors.lastname: Halliwell
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018384:Oxidative Stress
chemical_list: D008054:Lipid Peroxides; D009419:Nerve Tissue Proteins; D004247:DNA