Accumulation of C-terminally truncated tau protein associated with vulnerability of the perforant pathway in early stages of neurofibrillary pathology in Alzheimer's disease
Accumulation of C-terminally truncated tau protein associated with vulnerability of the perforant pathway in early stages of neurofibrillary pathology in Alzheimer's disease
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DOI：
10.1016/s0891-0618(01)00096-5
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发表时间：
2001-07-01
影响因子：
2.8
通讯作者：
Mena, R
中科院分区：
文献类型：
--
作者：
García-Sierra, F;Wischik, CM;Mena, R
神经病理学是阿尔茨海默病的特征性标志，与认知能力下降密切相关。我们已经分析了密度和分布的神经纤维缠结（NFT）的免疫反应与单克隆抗体（mAb）423在一个前瞻性分析的人口阿尔茨海默氏病（AD）的情况下，年龄匹配的控制。NFT在异皮质和同皮质区进行了检查，并与Braak病理分期和痴呆的临床严重程度相关。使用mAb 423，因为其识别作为NFT的主要成分的C-末端截短的tau片段。我们的研究结果表明，细胞外NFT和细胞内NFT在较小程度上与Braak分期和严重程度的临床指数显著相关。此外，两种类型的缠结的差异分布表明，第二层的内嗅皮层和transentorhinal区是特别容易受到神经退行性变。这些区域作为同皮质和海马体之间的连接点。因此，我们的研究结果表明，穿孔通路可能受到AD中截短tau蛋白积累的显著影响，这代表了痴呆临床严重程度的神经病理学预测因子。当通过用mAb 423和Alz-50以及染料噻嗪红的组合标记来检查神经病理学时，我们能够证明tau聚集的各个阶段。不同的阶段可能代表了一系列的构象变化，tau蛋白在缠结形成过程中经历的异体皮质在AD痴呆的早期发展。(C)2001 Elsevier Science B. V.保留所有权利。
Neurofibrillary pathology is a characteristic hallmark of Alzheimer's disease that is closely correlated with cognitive decline. We have analysed the density and distribution of neurofibrillary tangles (NFTs) that are immunoreactive with the monoclonal antibody (mAb) 423 in a prospectively analysed population of Alzheimer's disease (AD) cases and age-matched controls. NFTs were examined in allocortical and isocortical areas and correlated with Braak pathological stage and clinical severity of dementia. The mAb 423 was used as it recognises a C-terminally truncated tau fragment that is a major constituent of NFTs. Our results show that extracellular NFTs and, to a lesser extent, intracellular NFTs, correlated significantly with both Braak stages and the clinical index of severity. Furthermore, a differential distribution of the two types of tangles indicates that layer II of the entorhinal cortex and the transentorhinal area are particularly vulnerable to neurofibrillary degeneration. These areas serve as a point of connection between isocortex and hippocampus. Our findings, therefore, suggest that the perforant pathway may be substantially affected by the accumulation of truncated tau protein in AD and that this represents a neuropathological predictor for the clinical severity of dementia. When neurofibrillary pathology was examined by combined labelling with mAbs 423 and Alz-50 and the dye thiazin red, we were able to demonstrate various stages of tau aggregation. The different stages may represent a sequence of conformational changes that tau proteins undergo during tangle formation in the allocortex during the early development of dementia in AD. (C) 2001 Elsevier Science B.V. All rights reserved.