Department of Neuropsychiatry, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
Neurobiol Dis. 2010 Mar;37(3):731-7. doi: 10.1016/j.nbd.2009.12.012. Epub 2009 Dec 23.
In an analysis of amyloid pathology in Alzheimer disease, we used an in situ approach to identify amyloid-beta (Abeta) accumulation and oxidative damage to nucleic acids in postmortem brain tissue of the hippocampal formation from subjects with Alzheimer disease. When carboxyl-terminal-specific antibodies directed against Abeta40 and Abeta42 were used for immunocytochemical analyses, Abeta42 was especially apparent within the neuronal cytoplasm, at sites not detected by the antibody specific to Abeta-oligomer. In comparison to the Abeta42-positive neurons, neurons bearing oxidative damage to nucleic acids were more widely distributed in the hippocampus. Comparative density measurements of the immunoreactivity revealed that levels of intraneuronal Abeta42 were inversely correlated with levels of intraneuronal 8-hydroxyguanosine, an oxidized nucleoside (r=- 0.61, p<0.02). Together with recent evidence that the Abeta peptide can act as an antioxidant, these results suggest that intraneuronal accumulation of non-oligomeric Abeta may be a compensatory response in neurons to oxidative stress in Alzheimer disease.
在一项阿尔茨海默病淀粉样蛋白病理学分析中，我们采用原位分析方法，检测了阿尔茨海默病患者海马组织中淀粉样β（Abeta）的积累和核酸的氧化损伤。当使用针对 Abeta40 和 Abeta42 的羧基末端特异性抗体进行免疫细胞化学分析时，Abeta42 特别明显地存在于神经元细胞质中，而在针对 Abeta-寡聚物的抗体检测不到的部位。与 Abeta42 阳性神经元相比，携带核酸氧化损伤的神经元在海马中分布更为广泛。免疫反应性的比较密度测量显示，神经元内 Abeta42 的水平与神经元内 8-羟基鸟嘌呤（一种氧化核苷）的水平呈负相关（r=-0.61，p<0.02）。最近有证据表明 Abeta 肽可以作为一种抗氧化剂，这些结果表明，阿尔茨海默病中神经元内非寡聚 Abeta 的积累可能是神经元对氧化应激的一种代偿反应。
