The pathogenesis of Alzheimer's disease: a reevaluation of the "amyloid cascade hypothesis".
The pathogenesis of Alzheimer's disease: a reevaluation of the "amyloid cascade hypothesis".
复制标题
DOI：
10.4061/2011/630865
复制
发表时间：
2011-02-07
影响因子：
--
通讯作者：
Armstrong RA
中科院分区：
文献类型：
--
作者：
Armstrong RA
解释阿尔茨海默病（AD）发病机制最具影响力的理论是1992年首次提出的“淀粉样蛋白级联假说”（ACH）。ACH提出β-淀粉样蛋白（Aβ）沉积是AD的初始病理事件，导致老年斑（SPs）的形成，进而导致神经元的神经原纤维缠结（nft）死亡，最终导致痴呆。本文探讨了关于ACH的两个问题：(1)SPs和nft的发病机制之间是否存在关系，(2)这些病变与疾病发病机制的关系是什么？这些问题与SPs和nft的形态学和分子决定因素的研究、基因突变的影响、头部损伤引起的变性、实验诱导的脑病变的影响、转基因研究和解剖途径的变性有关。由此得出结论，sp和nft是独立发展的，可能是AD神经退行性变的产物而不是原因。对乙酰胆碱ACH的修饰可能更好地解释AD的发病机制，特别是迟发性AD病例。
The most influential theory to explain the pathogenesis of Alzheimer's disease (AD) has been the “Amyloid Cascade Hypothesis” (ACH) first formulated in 1992. The ACH proposes that the deposition of β-amyloid (Aβ) is the initial pathological event in AD leading to the formation of senile plaques (SPs) and then to neurofibrillary tangles (NFTs) death of neurons, and ultimately dementia. This paper examines two questions regarding the ACH: (1) is there a relationship between the pathogenesis of SPs and NFTs, and (2) what is the relationship of these lesions to disease pathogenesis? These questions are examined in relation to studies of the morphology and molecular determinants of SPs and NFTs, the effects of gene mutation, degeneration induced by head injury, the effects of experimentally induced brain lesions, transgenic studies, and the degeneration of anatomical pathways. It was concluded that SPs and NFTs develop independently and may be the products rather than the causes of neurodegeneration in AD. A modification to the ACH is proposed which may better explain the pathogenesis of AD, especially of late-onset cases of the disease.