Stereologic analysis of neurofibrillary tangle formation in prefrontal cortex area 9 in aging and Alzheimer's disease
Stereologic analysis of neurofibrillary tangle formation in prefrontal cortex area 9 in aging and Alzheimer's disease
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DOI：
10.1016/s0306-4522(02)00942-9
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Hof, PR
中科院分区：
文献类型：
--
作者：
Bussière, T;Gold, G;Hof, PR
阿尔茨海默病（AD）的神经病理学特征包括大脑皮层广泛的神经元死亡。事实上，虽然局限于海马体形成的神经病理变化是与年龄相关的记忆障碍的一致反映，但明显的痴呆只存在于新皮层受损伤的病例中。一些定量研究已经报道了这些区域的大量神经元损失和神经原纤维缠结（NFT）数量的平行增加。然而，缺乏关于NFT形成动力学的准确定量数据。在本研究中，我们对Brodmann前额叶皮层区9的III层深部（IIIc层）和V层浅部（Va层）的细胞内和细胞外（鬼）NFT和未受影响的神经元的比例进行了立体分析。将老年认知功能未受损病例与不同程度认知功能障碍病例进行比较。数据显示两层之间细胞内和细胞外NFT的形成速率不同，并证实存在与疾病相关的严重神经元丢失，但与年龄无关。研究还表明，在两个新皮层中，大量锥体细胞可能不受影响或处于NFT形成的过渡阶段。这些结果表明，直到阿尔茨海默病病程晚期，新皮层中存在相当数量的含有细胞内NFT的神经元。虽然不可能评估这些移行神经元是否具有完全的功能，但这些受影响的神经元可能对旨在保护阿尔茨海默病中容易发生神经原纤维变性的细胞的治疗策略有积极的反应。(c) 2003年。Elsevier Science Ltd.出版。版权所有。
Alzheimer's disease (AD) is characterized neuro-pathologically by several features including extensive neuronal death in the cerebral cortex. In fact, while neuropathological changes restricted to the hippocampal formation are a consistent reflection of age-related memory impairment, overt dementia is present only in cases with neocortical involvement. Several quantitative studies have reported a substantial loss of neurons from these regions and a parallel increase in the number of neurofibrillary tangles (NFT). However, accurate quantitative data on the dynamics of NFT formation are lacking. In the present study, we performed a stereologic analysis of the proportions of intracellular and extracellular (ghost) NFT, and unaffected neurons in the deep part of layer III (layer IIIc) and the superficial part of layer V (layer Va) of Brodmann's prefrontal cortex area 9. Elderly cognitively unimpaired cases were compared with cases with different degrees of cognitive dysfunction. The data revealed differential rates of formation of intracellular and extracellular NFT between the two layers, and confirmed the presence of a severe disease-associated, but not age-related, neuronal loss. It was also shown that a susbtantial number of pyramidal cells may persist either unaffected or in a transitional stage of NFT formation in both neocortical layers.These results suggest that a considerable number of neurons containing an intracellular NFT exists in the neocortex until late in the course of AD. Whereas it is not possible to assess whether such transitional neurons are fully functional, these affected neurons might respond positively to therapeutic strategies aimed at protecting the cells that are prone to neurofibrillary degeneration in AD. (C) 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.