BRAIN REGIONAL CORRESPONDENCE BETWEEN ALZHEIMERS-DISEASE HISTOPATHOLOGY AND BIOMARKERS OF PROTEIN OXIDATION

Four biomarkers of neuronal protein oxidation [W/S ratio of MAL-6 spin -labeled synaptosomes, phenylhydrazine-reactive protein carbonyl conte nt, glutamine synthetase (GS) activity, creatine kinase (CK) activity] in three brain regions [cerebellum, inferior parietal lobule (IPL), a nd hippocampus (HIP)] of Alzheimer's disease (AD)-demented and age-mat ched control subjects were assessed. These endpoints indicate that AD brain protein may be more oxidized than that of control subjects. The W/S ratios of AD hippocampal and inferior parietal synaptosomes are 30 and 46% lower, respectively, than corresponding values of tissue isol ated from control brain; however, the difference between the W/S ratio s of AD and control cerebellar synaptosomes is not significant. Protei n carbonyl content is increased 42 and 37% in the Alzheimer's HIP and IPL regions, respectively, relative to AD cerebellum, whereas carbonyl content in control HIP and IPL is similar to that of control cerebell um. GS activity decreases an average of 27% in the AD brain; CK activi ty declines by 80%. The brain regional variation of these oxidation-se nsitive biomarkers corresponds to established histopathological featur es of AD (senile plaque and neurofibrillary tangle densities) and is p aralleled by an increase in immunoreactive microglia. These data indic ate that senile plaque-dense regions of the AD brain may represent env ironments of elevated oxidative stress.