The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons.
The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons.
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DOI：
10.1097/nen.0b013e318248e614
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发表时间：
2012-03
影响因子：
3.2
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Nunomura A;Tamaoki T;Motohashi N;Nakamura M;McKeel DW Jr;Tabaton M;Lee HG;Smith MA;Perry G;Zhu X
虽然神经元RNA氧化是与年龄相关的神经退行性疾病如阿尔茨海默病（AD）的一个突出和确定的特征，但在衰老和从正常老年人到AD发作的过渡阶段对神经元RNA的氧化损伤尚未得到充分研究。在这项研究中，我们使用了原位方法，以确定一个氧化的RNA核苷8-羟基鸟苷（8 OHG）在大脑皮层的65个人没有痴呆症的年龄范围从0.3至86岁。我们还检查了来自20名老年人的脑样本，这些老年人被评估了他们的生前临床痴呆评定评分和死后脑病理诊断，以调查临床前AD和轻度认知障碍。8 OHG-免疫反应性的相对密度测量结果显示，海马和颞叶新皮质衰老过程中神经元RNA氧化有统计学意义的增加。在轻度认知障碍但非临床前AD的受试者中，与年龄匹配的对照组相比，颞叶皮质神经元显示出更高的氧化RNA负荷。这些结果表明，虽然神经元RNA氧化从根本上发生作为一个年龄相关的现象，更突出的RNA损伤比在正常老化与AD的前驱期的认知功能障碍的发作。
Although neuronal RNA oxidation is a prominent and established feature in age-associated neurodegenerative disorders such as Alzheimer disease (AD), oxidative damage to neuronal RNA in aging and in the transitional stages from normal elderly to the onset of AD has not been fully examined. In this study, we used an in situ approach to identify an oxidized RNA nucleoside 8-hydroxyguanosine (8OHG) in the cerebral cortex of 65 individuals without dementia ranging in age from 0.3 to 86 years. We also examined brain samples from 20 elderly who were evaluated for their premortem clinical dementia rating score and postmortem brain pathological diagnoses to investigate preclinical AD and mild cognitive impairment. Relative density measurements of 8OHG-immunoreactivity revealed a statistically significant increase in neuronal RNA oxidation during aging in the hippocampus and the temporal neocortex. In subjects with mild cognitive impairment but not preclinical AD, neurons of the temporal cortex showed a higher burden of oxidized RNA compared to age-matched controls. These results indicate that although neuronal RNA oxidation fundamentally occurs as an age-associated phenomenon, more prominent RNA damage than in normal aging correlates with the onset of cognitive impairment in the prodromal stage of AD.