α-internexin immunoreactivity reflects variable neuronal vulnerability in Alzheimer's disease and supports the role of the β-amyloid plaques in inducing neuronal injury
α-internexin immunoreactivity reflects variable neuronal vulnerability in Alzheimer's disease and supports the role of the β-amyloid plaques in inducing neuronal injury
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DOI：
10.1016/j.nbd.2004.10.001
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发表时间：
2005-03-01
影响因子：
6.1
通讯作者：
Vickers, JC
中科院分区：
文献类型：
--
作者：
Dickson, TC;Chuckowree, JA;Vickers, JC
本研究探讨了α-internexin在阿尔茨海默病（AD）中与β-淀粉样斑块形成相关的神经元改变中的作用。皮质神经元可通过其神经丝（NF）三联体和α-interexin蛋白的可变含量来定义，具有单独含有α-interexin的颗粒上锥体细胞的独特群体。在实验性创伤模型中，NF三联体和α-interexin均定位于物理损伤神经元的反应性轴突结构。类似地，NF三联体和α-interexin免疫反应性神经突在临床前AD病例中定位于密集填充有β-淀粉样纤维的斑块，表明某些斑块可能导致结构损伤或局部轴突运输障碍。然而，α-internexin，而不是NF三联体，环状反应性神经突存在于终末期AD病例中，表明选择性含有α-internexin的神经元相对较晚参与。这些结果暗示了特定的中间丝蛋白的表达在一个不同层次的差异神经元的脆弱性，以AD。(C)2004爱思唯尔公司All rights reserved.
This study investigated the role of alpha-internexin in the neuronal alterations associated with beta-amyloid plaque formation in Alzheimer's disease (AD). Cortical neurons could be defined by their variable content of neurofilament (NF) triplet and alpha-internexin proteins, with a distinct population of supragranular pyramidal cells containing alpha-internexin alone. Both NF triplet and alpha-internexin were localized to reactive axonal structures in physically damaged neurons in experimental trauma models. Similarly, NF triplet and alpha-internexin immunoreactive neurites were localized to plaques densely packed with beta-amyloid fibrils in preclinical AD cases, indicating that certain plaques may cause structural injury or impediment of local axonal transport. However, alpha-internexin, and not NF triplet, ring-like reactive neurites were present in end-stage AD cases, indicating the relatively late involvement of neurons that selectively contain alpha-internexin. These results implicate the expression of specific intermediate filament proteins in a distinct hierarchy of differential neuronal vulnerability to AD. (C) 2004 Elsevier Inc. All rights reserved.