Plaque-induced neurite abnormalities: Implications for disruption of neural networks in Alzheimer's disease
Plaque-induced neurite abnormalities: Implications for disruption of neural networks in Alzheimer's disease
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DOI：
10.1073/pnas.96.9.5274
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发表时间：
1999-04-27
影响因子：
11.1
通讯作者：
Hyman, BT
中科院分区：
文献类型：
--
作者：
Knowles, RB;Wyart, C;Hyman, BT
阿尔茨海默病患者的大脑含有细胞外 Aβ 淀粉样蛋白沉积物（老年斑）。尽管遗传证据表明 Aβ 沉积与该疾病存在因果关系，但 Aβ 破坏皮质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 Aβ 沉积物的神经元过程可能具有根本改变的形态。我们对这种形态改变的电生理效应进行了建模，并发现了平均斑块上几毫秒的预测延迟。我们认为，这种类型的延迟在整个新皮质区域的数千个斑块中发生，扰乱了动作电位的精确时间放电模式，直接导致神经系统衰竭和痴呆。
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 function 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.