The frequency of point mutations in mitochondrial DNA is elevated in the Alzheimer's brain

The frequency of point mutations in mitochondrial DNA is elevated in the Alzheimer's brain
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DOI:
10.1006/bbrc.2000.2885
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发表时间:
2000-06-24
影响因子:
3.1
通讯作者:
Zassenhaus, HP
Zassenhaus, HP
中科院分区:
生物学4区
文献类型:
--
作者:
Chang, SW;Zhang, DK;Zassenhaus, HP

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使用PCR为基础的策略,我们发现,线粒体DNA(mtDNA)的点突变频率是2- 3倍高的顶叶回,海马,小脑与阿尔茨海默病(AD)的受试者相比,正常对照。与此相反,通常研究的缺失突变mtDNA(4977)的水平在AD中没有升高。点突变的频率在三个脑区之间没有显著差异,而mtDNA(4977)的频率在小脑中比皮层低15- 25倍;这种区域差异在正常和阿尔茨海默氏症的大脑中都可以看到。在血液mtDNA中,点突变频率在AD患者中没有升高。所有三个脑区点突变频率的升高与氧化应激增加与AD相关的观点一致,(C)2000学术出版社。
Using a PCR-based strategy, we found that point mutation frequencies in mitochondrial DNA (mtDNA)were 2- to 3-fold higher in the parietal gyrus, hippocampus, and cerebellum from subjects with Alzheimer's disease (AD) compared to normal controls. In contrast, levels of a commonly studied deletion mutation, mtDNA(4977), were not elevated in AD. The frequency of point mutations did not vary significantly among the three brain areas, whereas the frequency of mtDNA(4977) was 15- to 25-fold lower in the cerebellum in comparison to the cortex; this regional variation was seen in both the normal and Alzheimer's brain. In blood mtDNA, point mutation frequencies were not elevated in AD patients. The elevated frequency of point mutations in all three brain regions is consistent with the idea that increased oxidant stress is associated with AD, (C) 2000 Academic Press.