McIntosh L J, Trush M A, Troncoso J C
Department of Biological Sciences, Stanford University, CA 94305, USA.
Free Radic Biol Med. 1997;23(2):183-90. doi: 10.1016/s0891-5849(96)00573-4.
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.
活性氧介导的过程被认为与阿尔茨海默病（AD）的发病机制有关。为了验证这一假设，我们研究了11对AD病例和年龄、死后延迟时间及组织保存时间相匹配的对照个体的尸检组织。对严重受AD病理影响的颞叶新皮质和未受影响的小脑进行脂质过氧化（LPO）组织标志物分析。在无金属离子或抗坏血酸等催化剂存在的情况下，组织匀浆在3小时孵育过程中因化学键断裂形成的平均化学发光，在AD颞叶皮质中显著增加，达到匹配对照的130%。两组间LPO产物（硫代巴比妥酸反应性物质——TBARS）的基础组织含量无差异。然而，孵育后AD颞叶皮质中的TBARS显著升高，达到对照的135%。相比之下，小脑中AD组织与对照组织无差异，表明存在疾病特异性的组织效应。由于口服抗氧化剂在过去几年中受到了相当多的关注，一名服用每日维生素E补充剂4年的AD患者的测试结果尤其有趣。与所有其他样本相比，颞叶皮质中CL反应性的时间进程明显延迟。这一观察结果与组织内抗氧化剂会淬灭ROS介导反应的假设一致。这项研究表明，AD颞叶皮质对ROS的敏感性增加，这可能有助于疾病的发病机制。此外，我们的观察结果表明，口服抗氧化剂补充剂可能对人类大脑中的LPO具有保护作用。
