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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Plaque-induced neurite abnormalities: Implications for disruption of neural networks in Alzheimer's disease
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Plaque-induced neurite abnormalities: Implications for disruption of neural networks in Alzheimer's disease

机译：斑块诱发的神经突异常：阿尔茨海默氏病对神经网络破坏的影响。

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摘要

The brains of Alzheimer's disease patients contain extracellular A#beta# amyloid deposits (senile plaques). Although genetic evidence causally links A#beta# deposition to the disease, the mechanism by which A#beta# disrupts cortical func- tion is unknown. Using triple immunofluorescent confocal microscopy and three-dimensional reconstructions, we found that neuronal processes that cross through an A#beta# deposit are likely to have a radically changed morphology. We modeled the electrophysiological effect of this changed morphology and found a predicted delay of several milliseconds over an average plaque. We propose that this type of delay, played out among thousands of plaques throughout neocortical areas, disrupts the precise temporal firing patterns of action potentials, contributing directly to neural system failure and dementia.
机译：阿尔茨海默氏病患者的大脑含有细胞外A＃beta＃淀粉样蛋白沉积物（老年斑）。尽管遗传证据将A＃beta＃沉积与疾病相关，但A＃beta＃破坏皮层功能的机制尚不清楚。使用三重免疫荧光共聚焦显微镜和三维重建，我们发现穿过A＃beta＃沉积物的神经元过程可能具有根本改变的形态。我们对这种变化的形态的电生理效应进行了建模，发现在平均噬菌斑上的延迟预计为数毫秒。我们建议这种类型的延迟发生在整个新皮层区域的数千个斑块中，破坏了动作电位的精确时间触发模式，直接导致了神经系统衰竭和痴呆。

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