INCREASED SUSCEPTIBILITY OF ALZHEIMERS-DISEASE TEMPORAL CORTEX TO OXYGEN-FREE RADICAL-MEDIATED PROCESSES

Reactive oxygen-mediated processes are thought to contribute to the pa thogenesis of Alzheimer's disease (AD). To investigate this hypothesis we studied autopsy tissue from Il pairs of AD cases and control indiv iduals matched for age, postmortem delay, and tissue storage time. The temporal neocortex, which is severely involved by AD pathology, and t he cerebellum, which is spared, were analyzed for tissue markers of li pid peroxidation (LPO). The average chemiluminescence formed from bond breakage in tissue homogenates during a 3-h incubation, without the p resence of catalysts such as metal ions or ascorbate, was significantl y increased in the AD temporal cortex to 130% of matched controls. Bas al tissue content of LPO products (thiobarbituric acid reactive substa nces-TBARs) was not different between groups. However, TBARs were sign ificantly elevated in AD temporal cortex to 135% of control after the incubation. In contrast, in the cerebellum there was no difference bet ween AD and control tissue, indicating a disease-specific tissue effec t. Because the use of oral antioxidants have received considerable att ention in the last few years, the results seen in the testing of an AD patient who took daily vitamin E supplements for 4 years is particula rly interesting. The time course for CL reactivity in the temporal cor tex was considerably delayed compared to all other samples. This obser vation is consistent with the hypothesis that antioxidants within tiss ue will quench ROS-mediated reactions. This study indicates that there is increased susceptibility to ROS in the AD temporal cortex that may contribute to the pathogenesis of the disease. Furthermore, our obser vations suggest that oral antioxidant supplementation may be protectiv e against LPO in the human brain. (C) 1997 Elsevier Science Inc.