Braak E, Braak H, Mandelkow E M
Zentrum der Morphologie, J.W. Goethe-Universität, Frankfurt/Main, Germany.
Acta Neuropathol. 1994;87(6):554-67. doi: 10.1007/BF00293315.
Frontal sections of the temporal lobe including the transentorhinal/entorhinal region, amygdala, and/or hippocampus from human adult brains are studied for cytoskeleton changes using immunostaining with the antibodies AT8 and Alz-50 and selective silver impregnation methods for neurofibrillary changes of the Alzheimer type. For the purpose of correlation, the two methods are carried out one after the other on the same section. Layer pre-alpha in the transentorhinal/entorhinal region harbours nerve cells which are among the first nerve cells in the entire brain to show the development of neurofibrillary changes. This presents the opportunity for study of both early events in the destruction of the cytoskeleton in individual neurons, and to relate changes which occur in the neuronal processes in the absence of alterations in their immediate surroundings to those happening in the soma. Immunoreactions with the AT8 antibody in particular reveal a clear sequence of changes in the neuronal cytoskeleton. Group 1 neurons present initial cytoskeleton changes in that the soma, dendrites, and axon are completely marked by granular AT8 immunoreactive material. These neurons appear quite normal and turn out to be devoid of argyrophilic material when observed in silver-stained sections. Group 2 neurons show changes in the cellular processes. The terminal tuft of the apical dendrite is replaced by tortuous varicose fibres and coarse granules. The distal portions of the dendrites are curved and show appendages and thickened portions. Intensely homogeneously immunostained rod-like inclusions are encountered in these thickened portions and in the soma. A number of these rod-like inclusions are visible after silver staining, as well. Group 3 neurons display even more pronounced alterations of their distal--most dendritic portions. The intermediate dendritic parts lose immunoreactivity, but the soma is homogeneously immunostained. Silver staining reveals in most of the distal dendritic parts neuropil threads, and in the soma a classic neurofibrillary tangle. Group 4 structures are marked by accumulations of coarse AT8-immunoreactive granules. Silver staining provides evidence that the fibrillary material has become an extraneuronal, "early" ghost tangle. Finally, group 5 structures present "late" ghost tangles in silver-stained sections but fail to demonstrate AT8 immunoreactivity. It is suggested that the altered tau protein shown by the antibody AT8 represents an early cytoskeleton change which eventually leads to the formation of argyrophilic neurofibrillary tangles and neuropil threads.
对来自成年人类大脑的颞叶额叶切片进行研究，这些切片包括内嗅/嗅周区域、杏仁核和/或海马体，采用抗体AT8和Alz - 50免疫染色以及针对阿尔茨海默型神经原纤维变化的选择性银浸染方法，来观察细胞骨架的变化。为了进行相关性研究，这两种方法在同一切片上先后进行。内嗅/嗅周区域的前α层含有神经细胞，这些神经细胞是全脑最早出现神经原纤维变化的神经细胞之一。这为研究单个神经元中细胞骨架破坏的早期事件提供了机会，也有助于将神经元突起中在其紧邻周围环境未发生改变时出现的变化，与胞体中发生的变化联系起来。特别是与AT8抗体的免疫反应揭示了神经元细胞骨架变化的清晰序列。第1组神经元呈现出细胞骨架的初始变化，即胞体、树突和轴突完全被颗粒状的AT8免疫反应性物质标记。这些神经元看起来相当正常，在银染切片中观察时发现它们没有嗜银物质。第2组神经元在细胞突起中表现出变化。顶树突的终末簇被扭曲的曲张纤维和粗大颗粒取代。树突的远端部分弯曲，有附属物和增厚部分。在这些增厚部分和胞体中可遇到强烈均匀免疫染色的棒状包涵体。银染后也能看到一些这样的棒状包涵体。第3组神经元在其最远端的树突部分表现出更明显的改变。中间树突部分失去免疫反应性，但胞体被均匀免疫染色。银染显示在大多数远端树突部分有神经毡丝，在胞体中有典型的神经原纤维缠结。第4组结构以粗大的AT8免疫反应性颗粒聚集为特征。银染证明纤维状物质已变成细胞外的“早期”幽灵缠结。最后，第5组结构在银染切片中呈现“晚期”幽灵缠结，但未显示AT8免疫反应性。研究表明，抗体AT8所显示的改变的tau蛋白代表细胞骨架的早期变化，最终导致嗜银性神经原纤维缠结和神经毡丝的形成。
