Neuronal RNA oxidation is a prominent feature of familial Alzheimer's disease
Neuronal RNA oxidation is a prominent feature of familial Alzheimer's disease
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DOI：
10.1016/j.nbd.2004.06.003
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发表时间：
2004-10-01
影响因子：
6.1
通讯作者：
Perry, G
中科院分区：
文献类型：
--
作者：
Nunomura, A;Chiba, S;Perry, G
应用原位杂交技术，对13例年龄47-81岁、伴有早老素-1（PS-1）或淀粉样蛋白前体（AOPP）基因突变的家族性Alzheimer病（FAD）患者的额叶皮质进行了8-羟基鸟苷（8-OHG）的检测。在FAD的上级和中额回内广泛分布有胞浆内80 HG免疫反应阳性的神经元。神经元80 HG免疫反应性的相对强度测量显示，与对照组（n = 15，年龄59-81岁）相比，FAD显著增加，而PS-1和AOPP FAD之间的相对80 HG没有差异。有趣的是，一个携带PS-1突变的前驱病例显示出相当高的相对80 HG水平，而FAD中神经元80 HG水平的增加在具有较低百分比面积的Abeta 42负荷的病例中更为突出。这些结果表明，氧化应激是参与FAD病理级联反应的早期事件。(C)2004年爱思唯尔公司All rights reserved.
An in situ approach was used to identify the oxidized RNA nucleoside 8-hydroxyguanosine (8OHG) in the frontal cortex of familial Alzheimer's disease (FAD) with a mutation in presenilin-1 (PS-1) or amyloid protein precursor (AOPP) gene (n = 13, age 47-81 years). Neurons with marked 80HG immunoreaction in the cytoplasm were widely distributed in the superior/middle frontal gyros of FAD. Relative intensity measurements of neuronal 80HG immunoreactivity showed that there was a significant increase in FAD compared with controls (n = 15, age 59-81 years), while there was no difference in relative 80HG between the PS-1 and the AOPP FAD. Interestingly, a presymptomatic case carrying a PS-1 mutation showed a considerable level of relative 8OHG, and the increased levels of neuronal 80HG in FAD were more prominent in cases with a lower percentage area of Abeta42 burden. These results suggest that oxidative stress is an early event involved in the pathological cascade of FAD. (C) 2004 Elsevier Inc. All rights reserved.