Reduction of acetylated alpha-tubulin immunoreactivity in neurofibrillary tangle-bearing neurons in Alzheimer's disease
Reduction of acetylated alpha-tubulin immunoreactivity in neurofibrillary tangle-bearing neurons in Alzheimer's disease
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DOI：
10.1097/00005072-199609000-00003
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发表时间：
1996-09-01
影响因子：
3.2
通讯作者：
Brion, JP
中科院分区：
文献类型：
--
作者：
Hempen, B;Brion, JP
在含有神经原纤维缠结（NFT）的神经元中，微管网络的紊乱被认为是导致含NFT神经元功能障碍的核心生理病理机制，神经原纤维缠结是阿尔茨海默病的特征性神经病理病变之一。“成对螺旋丝 - tau”（NFT的主要蛋白质成分）在受影响神经元中的积累被认为会导致这些细胞中微管稳定性下降。为了进一步探究阿尔茨海默病中微管稳定性下降的假说，我们在本研究中调查了具有不同数量NFT的神经元中稳定微管的相对含量。我们使用了一种双重免疫细胞化学标记技术，用抗tau抗体（作为NFT的标记）和抗乙酰化α - 微管蛋白抗体（作为稳定微管的标记），并在半定量尺度上对同一神经元中的tau和乙酰化α - 微管蛋白免疫反应性进行评级。我们观察到大多数含NFT的神经元中乙酰化α - 微管蛋白免疫反应性显著降低；tau和乙酰化α - 微管蛋白免疫反应性之间存在统计学关系，表明神经元中tau免疫反应性NFT的存在与微管蛋白免疫反应性之间呈反比关系。这种降低在tau免疫反应性相对较低的神经元群体中就已出现，这表明乙酰化α - 微管蛋白免疫反应性的降低以及微管稳定性的降低可能是这些细胞中的早期事件。
A disturbance of the microtubule network in neurons containing neurofibrillary tangles (NFT), one of the characteristic neuropathological lesions in Alzheimer's disease, has been advocated as a central physiopathological mechanism leading to neuronal dysfunction in NFT-containing neurons. The accumulation of ''paired helical filament-tau,'' the main proteineous component of NFT. in affected neurons has been proposed to induce a decrease of microtubule stability in these cells. To further explore the hypothesis of a decrease in microtubule stability in Alzheimer's disease, we have investigated in this study the relative content in stable microtubules in neurons with different amount of NFT. We used a double immunocytochemical labeling technique with antibodies to tau (as a marker of NFT) and to acetylated alpha-tubulin (as a marker of stable microtubules) and rated on a semi-quantitative scale the tan and acetylated alpha-tubulin-immunoreactivities in the same neurons. We observed a strong reduction in acetylated alpha-tubulin immunoreactivity in most NFT-bearing neurons; a statistical relationship between tau and acetylated alpha-tubulin immunoreactivity was demonstrated, assuming an inverse relationship between the presence of tau-immunoreactive NFT and tubulin-immunoreactivity in neurons. This reduction was already seen in the neuronal population with a relatively lower tau-immunoreactivity in, suggesting that reduction in acetylated alpha-tubulin immunoreactivity, and reduction in microtubule stability, could be an early event in these cells.