硫黄素 S 阳性淀粉样沉积物在转基因小鼠和阿尔茨海默病中的神经毒性作用。
Neurotoxic effects of thioflavin S-positive amyloid deposits in transgenic mice and Alzheimer's disease.
作者信息
Urbanc B, Cruz L, Le R, Sanders J, Ashe K Hsiao, Duff K, Stanley H E, Irizarry M C, Hyman B T
机构信息
Center for Polymer Studies and Department of Physics, Boston University, Boston, MA 02215, USA.
出版信息
Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):13990-5. doi: 10.1073/pnas.222433299. Epub 2002 Oct 9.
Abstract
Despite extensive deposition of putatively neurotoxic amyloid-beta (Abeta) protein in the brain, it has not been possible to demonstrate an association of Abeta deposits with neuronal loss in Alzheimer's disease (AD), and neuronal loss is minimal in transgenic mouse models of AD. Using triple immunostaining confocal microscopy and analyzing the images with the cross-correlation density map method from statistical physics, we directly compared Abeta deposition, Abeta morphology, and neuronal architecture. We found dramatic, focal neuronal toxicity associated primarily with thioflavin S-positive fibrillar Abeta deposits in both AD and PSAPP mice. These results, along with computer simulations, suggest that Abeta develops neurotoxic properties in vivo when it adopts a fibrillar beta-pleated sheet conformation.
摘要
尽管在大脑中存在大量推测具有神经毒性的β淀粉样蛋白（Aβ）沉积，但在阿尔茨海默病（AD）中，尚未证实Aβ沉积与神经元丢失之间存在关联，并且在AD转基因小鼠模型中神经元丢失极少。我们使用三重免疫染色共聚焦显微镜，并采用统计物理学中的互相关密度图方法对图像进行分析，直接比较了Aβ沉积、Aβ形态和神经元结构。我们发现，在AD和PSAPP小鼠中，显著的局灶性神经元毒性主要与硫黄素S阳性的纤维状Aβ沉积有关。这些结果以及计算机模拟表明，当Aβ采用纤维状β折叠片构象时，它在体内会产生神经毒性特性。
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