Alzheimer's disease: a re-examination of the amyloid hypothesis
Alzheimer's disease: a re-examination of the amyloid hypothesis
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DOI：
10.1016/s0166-2236(97)01168-5
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发表时间：
1998-01-01
影响因子：
15.9
通讯作者：
Robakis, NK
中科院分区：
文献类型：
--
作者：
Neve, RL;Robakis, NK
阿尔茨海默病(AD)是一种以神经性淀粉样斑块和神经原纤维缠结为特征的大脑神经退行性疾病，虽然它最常发生在老年人，但这种疾病也困扰较年轻的患者，大多数AD病例起病晚，缺乏明显的遗传病因，并以散发为特征，而少数病例起病较早，并在家庭内强烈分离(FAD)，提示遗传病因学。在过去的十年中，很明显，这种疾病的临床和组织病理表型是由不同的遗传因素，可能是环境因素引起的。事实上，有几个基因似乎共同导致了大多数家族性疾病，而载脂蛋白E(ApoE)基因的epsilon 4等位基因已被证明是迟发性AD的重要危险因素，尽管有这种异质性的证据，但已有证据表明，所有这些因素都通过一条共同的途径发挥作用，触发大脑中淀粉样蛋白的沉积，这最终导致AD神经元变性。然而，这是一个有争议的理论，主要是因为大脑中淀粉样变性的浓度和分布与AD病理的几个参数，包括痴呆的程度，之间的相关性很差。突触丢失，神经元丢失，细胞骨架异常。
Alzheimer's disease (AD) is a neurodegenerative disorder of the brain characterized by the presence of neuritic amyloid plaques and neurofibrillary tangles, Although it most frequently occurs in the elderly, this disorder also afflicts younger patients, The majority of AD cases are late in onset, lack an obvious genetic etiology and are characterized as sporadic, whereas a small percentage of cases are early in onset and segregate strongly within families (FAD), suggesting a genetic etiology, During the past decade it has become evident that the clinical and histopathological phenotypes of this disease are caused by heterogeneous genetic,and probably environmental,factors. Indeed, several genes have been identified that together appear to cause most of the familial forms of the disease, whereas the epsilon 4 allele of the apolipoprotein E (apoE) gene has been shown to be a significant risk factor for the late onset forms of AD Despite this evidence of heterogeneity, it has been suggested that all of these factors work through a common pathway by triggering the deposition of amyloid in the brain, which is ultimately responsible for the neuronal degeneration of AD, This is a controversial theory, however, primarily because there is a poor correlation between the concentrations and distribution of amyloid depositions in the brain and several parameters of AD pathology, including degree of dementia, loss of synapses, loss of neurons and abnormalities of the cytoskeleton.