Neurochemical diversity of dystrophic neurites in the early and late stages of Alzheimer's disease
Neurochemical diversity of dystrophic neurites in the early and late stages of Alzheimer's disease
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DOI：
10.1006/exnr.1998.7010
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发表时间：
1999-03-01
影响因子：
5.3
通讯作者：
Vickers, JC
中科院分区：
文献类型：
--
作者：
Dickson, TC;King, CE;Vickers, JC
我们研究了阿尔茨海默病早期和晚期与P-淀粉样斑块形成相关的异常神经突的神经化学和形态学多样性。临床前阿尔茨海默氏病的特点是存在异常的神经突含有神经丝或嗜铬粒蛋白A免疫反应。这些病例中所有成簇的营养不良性神经突均与淀粉样蛋白斑块相关。在临床前阿尔茨海默病的神经丝免疫反应性营养不良的神经突可以进一步细分为灯泡和环状结构，这些异常的神经突含有磷酸化和去磷酸化的神经丝表位。阿尔茨海默氏病中的营养不良神经突可以被细分为主要的神经丝、tau蛋白或嗜铬粒蛋白A免疫标记形式。一些神经丝免疫反应性神经突具有标记为tau的核心区域。阿尔茨海默氏病中营养不良神经突的神经丝具有与临床前病例中观察到的相同的磷酸化和去磷酸化依赖性表位。因此，一个异常积累的磷酸化神经丝代表最早的细胞骨架改变与营养不良的神经突形成。此外，这些数据表明，营养不良的神经突可以通过神经毒性丰富的形式"成熟"为含有标记为tau的深刻改变的细丝的神经突。与营养不良性神经突形成相关的精确形态学和神经化学变化表明，P-淀粉样蛋白斑块对周围轴突造成物理损伤。由此产生的轴突发芽和深刻的细胞骨架改变将遵循这种物理创伤的刻板反应的慢性刺激。(C)北京：科学出版社.
We examined the neurochemical and morphological diversity of abnormal neurites associated with P-amyloid plaque formation in the early and late stages of Alzheimer's disease. Preclinical Alzheimer's disease was characterised by the presence of abnormal neurites containing either neurofilament or chromogranin A immunoreactivity. All clustered dystrophic neurites in these cases were associated with p-amyloid plaques. Neurofilament immunoreactive dystrophic neurites in preclinical Alzheimer's disease could be further subclassified into bulb- and ring-like structures, and these abnormal neurites contained both phosphorylated and dephosphorylated neurofilament epitopes. Dystrophic neurites in Alzheimer's disease could be subdivided into predominantly neurofilament, tau, or chromogranin A immunolabeled forms. Some neurofilament immunoreactive neurites had a core region labeled for tau. The neurofilaments of the dystrophic neurites in Alzheimer's disease had the same complement of phosphorylation- and dephosphorylation-dependent epitopes as observed in preclinical cases. Therefore, an abnormal accumulation of variably phosphorylated neurofilaments represent the earliest cytoskeletal alteration associated with dystrophic neurite formation. Furthermore, these data indicate that dystrophic neurites may "mature" through neurofilament-abundant forms to the neurites containing the profoundly altered filaments labeled for tau. The precise morphological and neurochemical changes associated with dystrophic neurite formation suggests that P-amyloid plaques are causing physical damage to surrounding axons. The resultant axonal sprouting and profound cytoskeletal alterations would follow the chronic stimulation of the stereotypical reaction to such physical trauma. (C) 1999 Academic Press.