Increased susceptibility of Alzheimer's disease temporal cortex to oxygen free radical-mediated processes

Free Radic Biol Med. 1997;23(2):183-90. doi: 10.1016/s0891-5849(96)00573-4.

Abstract

Reactive oxygen-mediated processes are though to contribute to the pathogenesis of Alzheimer's disease (AD). To investigate this hypothesis we studied autopsy tissue from 11 pairs of AD cases and control individuals matched for age, postmortem delay, and tissue storage time. The temporal neocortex, which is severely involved by AD pathology, and the cerebellum, which is spared, were analyzed for tissue markers of lipid peroxidation (LPO). The average chemiluminescence formed from bond breakage in tissue homogenates during a 3-h incubation, without the presence of catalysts such as metal ions or ascorbate, was significantly increased in the AD temporal cortex to 130% of matched controls. Basal tissue content of LPO products (thiobarbituric acid reactive substances--TBARs) was not different between groups. However, TBARs were significantly elevated in AD temporal cortex to 135% of control after the incubation. In contrast, in the cerebellum there was no difference between AD and control tissue, indicating a disease-specific tissue effect. Because the use of oral antioxidants have received considerable attention 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 particularly interesting. The time course for CL reactivity in the temporal cortex was considerably delayed compared to all other samples. This observation is consistent with the hypothesis that antioxidants within tissue 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 observation suggest that oral antioxidant supplementation may be protective against LPO in the human brain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism*
  • Antioxidants / therapeutic use
  • Cerebellum / drug effects
  • Cerebellum / metabolism
  • Free Radicals / metabolism
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Lipid Peroxidation / drug effects
  • Luminescent Measurements
  • Middle Aged
  • Reactive Oxygen Species / metabolism*
  • Temporal Lobe / drug effects
  • Temporal Lobe / metabolism*
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Vitamin E / therapeutic use

Substances

  • Antioxidants
  • Free Radicals
  • Reactive Oxygen Species
  • Thiobarbituric Acid Reactive Substances
  • Vitamin E