Microtubule reduction in Alzheimer's disease and aging is independent of τ filament formation
Microtubule reduction in Alzheimer's disease and aging is independent of τ filament formation
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DOI：
10.1016/s0002-9440(10)64296-4
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发表时间：
2003-05-01
影响因子：
6
通讯作者：
Perry, G
中科院分区：
文献类型：
--
作者：
Cash, AD;Aliev, G;Perry, G
生物化学研究表明，磷酸化的T，如在成对螺旋丝（PHF）中发现的，不促进微管组装，导致PHF形成导致阿尔茨海默病（AD）中微管缺陷的观点。然而，虽然这个问题是最重要的方面，以进一步了解AD的细胞生物学，没有定量检查微管减少AD及其与PHFs的关系已经进行。为了直接研究这个问题，我们对AD和对照病例的脑活检标本进行了形态学研究。对神经元进行超微结构分析，以比较患病和对照病例神经元中的微管组装状态，并检查PHF积累的影响。我们发现，与对照组相比，AD锥体神经元中微管的数量和总长度均显著和选择性地减少（P = 0.000004），但微管密度的这种减少与PHFs惊人地无关（P = 0.8）。此外，我们发现对照组中微管密度随年龄增长而显著降低（P = 0.016）。这些结果表明，减少微管组装是不依赖于T异常的AD和老化。
Biochemical studies show that phosphorylated T, like that found in paired helical filaments (PHFs), does not promote microtubule assembly leading to the view that PHF formation leads to microtubule deficiency in Alzheimer's disease (AD). However, although this issue is one of the most important aspects to further understanding the cell biology of AD, no quantitative examination of microtubule diminution in AD and its relationship with PHFs has been performed. To examine this issue directly, we undertook a morphometric study of brain biopsy specimens from AD and control cases. Ultrastructural analysis of neurons was performed to compare the microtubule assembly state in neurons of diseased and control cases and to examine the effect of PHF accumulation. We found that both number and total length of microtubules were significantly and selectively reduced in pyramidal neurons from AD in comparison to control cases (P = 0.000004) but that this decrement in microtubule density was surprisingly unrelated to PHFs (P = 0.8). Further, we found a significant age-dependent decrease in microtubule density with aging in the control cases (P = 0.016). These findings suggest that reduction in microtubule assembly is not dependent on T abnormalities of AD and aging.