Selkoe D J
Neurobiol Aging. 1986 Nov-Dec;7(6):425-32. doi: 10.1016/0197-4580(86)90055-2.
The progressive dysfunction and loss of neurons in Alzheimer's disease (AD) is accompanied by marked structural changes in innumerable neuronal cell bodies and neurites, particularly in limbic and association cortices. Qualitatively indistinguishable neuronal lesions occur in much smaller numbers during normal aging. Highly insoluble paired helical filaments (PHF) and antigenically related straight filaments accumulate in perikaryal tangles and the neurites of neuritic plaques. In addition, PHF antibodies reveal the presence of PHF antigens in many individual cortical neurites not clustered into discrete plaques. Recent studies in several laboratories indicate that altered forms of the microtubule-associated phosphoprotein, tau, are important constituents of PHF. Other neuronal cytoskeletal proteins, particularly microtubule-associated protein 2 and neurofilament, have also been associated with PHF. In contrast, the extracellular amyloid filaments found in the centers of many neuritic plaques and in cortical and meningeal vessels appear to be composed of hydrophobic low molecular weight protein(s) distinct from PHF. A major question for further study regards the cellular origin and role of microvascular amyloid in the degeneration of neurites of multiple neurotransmitter specificities in AD cortex. The widespread neuritic and perikaryal alterations in brain tissue are likely to represent, at least in part, the morphological substrate of cortical dysfunction in AD.
阿尔茨海默病（AD）中神经元的进行性功能障碍和丧失伴随着无数神经元细胞体和神经突的显著结构变化，尤其是在边缘皮质和联合皮质。在正常衰老过程中，也会出现数量少得多的、在性质上难以区分的神经元损伤。高度不溶性的双螺旋丝（PHF）和抗原相关的直丝在核周缠结和神经炎性斑块的神经突中积聚。此外，PHF抗体显示，在许多未聚集成离散斑块的单个皮质神经突中也存在PHF抗原。几个实验室最近的研究表明，微管相关磷蛋白tau的改变形式是PHF的重要组成成分。其他神经元细胞骨架蛋白，特别是微管相关蛋白2和神经丝，也与PHF有关。相比之下，在许多神经炎性斑块中心以及皮质和脑膜血管中发现的细胞外淀粉样丝似乎由不同于PHF的疏水性低分子量蛋白质组成。一个有待进一步研究的主要问题是，微血管淀粉样蛋白在AD皮质中多种神经递质特异性神经突退变中的细胞起源和作用。脑组织中广泛的神经突和核周改变可能至少部分代表了AD中皮质功能障碍的形态学基础。
