Mitochondrial abnormalities in Alzheimer's disease
Mitochondrial abnormalities in Alzheimer's disease
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DOI：
10.1523/jneurosci.21-09-03017.2001
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发表时间：
2001-05-01
影响因子：
5.3
通讯作者：
Smith, MA
中科院分区：
文献类型：
--
作者：
Hirai, K;Aliev, G;Smith, MA
阿尔茨海默病中的氧化损伤，包括对核酸的氧化损伤，主要限于易感神经元群体的细胞质，这一发现表明线粒体异常可能是阿尔茨海默病慢性氧化应激谱的一部分。在这项研究中，我们使用线粒体DNA（mtDNA）原位杂交、细胞色素氧化酶免疫细胞化学和活检标本电子显微照片的形态测量来确定阿尔茨海默病中是否存在线粒体异常及其与8-羟基鸟苷标记的氧化损伤的关系。和硝基酪氨酸。我们发现，在阿尔茨海默病中显示氧化损伤增加的相同神经元在mtDNA和细胞色素氧化酶中有显著的增加。令人惊讶的是，大部分mtDNA和细胞色素氧化酶存在于神经元细胞质中，并且在mtDNA的情况下，空泡与脂褐质相关。形态学分析表明，线粒体在阿尔茨海默病中显著减少。线粒体异常和氧化损伤的部位和程度之间的关系表明，阿尔茨海默病的这些特征之间存在密切的早期联系。
The finding that oxidative damage, including that to nucleic acids, in Alzheimer's disease is primarily limited to the cytoplasm of susceptible neuronal populations suggests that mitochondrial abnormalities might be part of the spectrum of chronic oxidative stress of Alzheimer's disease. In this study, we used in situ hybridization to mitochondrial DNA (mtDNA), immunocytochemistry of cytochrome oxidase, and morphometry of electron micrographs of biopsy specimens to determine whether there are mitochondrial abnormalities in Alzheimer's disease and their relationship to oxidative damage marked by 8-hydroxyguanosine and nitrotyrosine. We found that the same neurons showing increased oxidative damage in Alzheimer's disease have a striking and significant increase in mtDNA and cytochrome oxidase. Surprisingly, much of the mtDNA and cytochrome oxidase is found in the neuronal cytoplasm and in the case of mtDNA, the vacuoles associated with lipofuscin. Morphometric analysis showed that mitochondria are significantly reduced in Alzheimer's disease. The relationship shown here between the site and extent of mitochondrial abnormalities and oxidative damage suggests an intimate and early association between these features in Alzheimer's disease.