Masliah E
Department of Neurosciences, University of California, San Diego, La Jolla 92093-0624, USA.
Histol Histopathol. 1995 Apr;10(2):509-19.
Alzheimer's disease (AD) is characterized by a progressive cognitive decline in which memory, initiation, learning and conceptualization are severely affected. The main histopathological alterations are the presence of amyloid beta/A4-containing plaques, tangles and amyloid angiopathy. It is believed that these brain alterations are associated with abnormal expression and/or processing of amyloid precursor protein (APP) and with abnormal assembly of cytoskeletal proteins. Recent quantitative studies with the electron microscope and with immunochemical/immunocytochemical assays, using molecular markers for synaptic proteins, have shown that synaptic loss in the cortex is the major correlate of the patterns of cognitive decline in AD. The synaptic loss in AD is accompanied by neuronal loss and aberrant sprouting, and studies in incipient AD cases have shown that this alteration occurs very early in the progression of the disease preceding tangle formation and neuronal loss. These results suggest that damage to the synaptic terminal plays a central role in the pathogenesis of AD. The mechanisms of synaptic pathology in AD are not yet clear, however, studies in transgenic animal models support the possibility that APP participates in synaptic stabilization and that abnormal metabolism of this molecule could lead to synaptic dysfunction which, in turn, results in neurodegeneration and dementia.
阿尔茨海默病（AD）的特征是进行性认知衰退，其中记忆、启动能力、学习和概念化能力受到严重影响。主要的组织病理学改变是含有β-淀粉样蛋白/A4的斑块、缠结和淀粉样血管病。据信，这些脑部改变与淀粉样前体蛋白（APP）的异常表达和/或加工以及细胞骨架蛋白的异常组装有关。最近使用突触蛋白分子标记物的电子显微镜以及免疫化学/免疫细胞化学分析的定量研究表明，皮质中的突触丧失是AD认知衰退模式的主要相关因素。AD中的突触丧失伴随着神经元丧失和异常出芽，对早期AD病例的研究表明，这种改变在疾病进展中非常早地发生，早于缠结形成和神经元丧失。这些结果表明，突触终末损伤在AD发病机制中起核心作用。然而，AD中突触病理学的机制尚不清楚，转基因动物模型的研究支持APP参与突触稳定的可能性，并且该分子的异常代谢可能导致突触功能障碍，进而导致神经退行性变和痴呆。
