Comparative epitope analysis of neuronal cytoskeletal proteins in Alzheimer's disease senile plaque neurites and neuropil threads.
Comparative epitope analysis of neuronal cytoskeletal proteins in Alzheimer's disease senile plaque neurites and neuropil threads.
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发表时间：
1991-03
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通讯作者：
M. L. Schmidt;V. Lee;J. Trojanowski
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作者：
M. L. Schmidt;V. Lee;J. Trojanowski
老年斑(SP)、冠状突起和神经束丝(NTS)中的营养不良性轴突大量聚集在阿尔茨海默病(AD)皮质中。因此，它们可能在AD的认知缺陷中起作用。然而，这些神经性病变的组成尚不清楚，也不知道它们来自轴突、树突还是两者兼而有之。为了深入了解AD中SP突起和NTS的组成和来源，我们进行了一项原位表位定位研究，我们使用278个针对神经丝(NF)每个亚基或微管相关蛋白(即tau和微管相关蛋白2)空间不同表位的单抗来探测这些损害。中分子NF-M和tau在SP突起中广泛表达，即从NH2延伸到NH2和tau的COOH结构域的表位。相反，微管相关蛋白2在任何SP中都不存在，在SP突起中只检测到Low核心区(NF-L)和高分子量亚基尾段的表位。SP核从未被这些抗体染色过。NTS与SP神经突起相似之处在于它们含有相同的tau表位，没有任何微管相关蛋白2免疫反应，但它们也不同，因为它们几乎不包含任何NF决定簇。这些SP神经突起和NTS之间的抗原差异表明，NTS和SP神经突起是明显独立的病变，反映了AD患者神经元细胞骨架的广泛破坏。
Dystrophic neurites in senile plaque (SP) coronas and neuropil threads (NTs) massively accumulate in Alzheimer's disease (AD) cortex. Hence, they may contribute to the cognitive deficits in AD. However, the composition of these neuritic lesions is poorly understood, and it is not known if they derive from axons, dendrites or both. To gain insights into the composition and derivation of SP neurites and NTs in AD, we undertook an in situ epitope mapping study wherein we probed these lesions using 278 monoclonal antibodies specific for spatially distinct epitopes in each neurofilament (NF) subunit, or in microtubule-associated proteins, i.e., tau and microtubule-associated protein 2. The middle molecular weight NF subunit (NF-M) and tau were extensively represented in SP neurites, i.e., epitopes extending from the NH2 to COOH domains of NF-M and tau were present. In contrast, microtubule-associated protein 2 was not present in any SPs, and only epitopes in the core domain of the low (NF-L), and in the tail piece of the high molecular weight subunit were detected in SP neurites. SP cores never stained with these antibodies. NTs were similar to SP neurites in that they contained the same complement of tau epitopes, and were devoid of any microtubule-associated protein 2 immunoreactivity, but they were also distinct because they rarely contained any NF determinants. These antigenic dissimilarities between SP neurites and NTs suggest that NTs and SP neurites are distinctly separate lesions that reflect widespread disruption of the neuronal cytoskeleton in AD.