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致命性头部损伤后β-淀粉样蛋白沉积是否存在遗传基础?

Is there a genetic basis for the deposition of beta-amyloid after fatal head injury?

作者信息

Graham D I, Gentleman S M, Nicoll J A, Royston M C, McKenzie J E, Roberts G W, Mrak R E, Griffin W S

机构信息

Department of Neuropathology, University of Glasgow, Scotland, U.K.

出版信息

Cell Mol Neurobiol. 1999 Feb;19(1):19-30. doi: 10.1023/a:1006956306099.

Abstract
  1. Alzheimer's disease is a heterogeneous disorder that may be caused by genetic or environmental factors or by a combination of both. Abnormalities in chromosomes 1, 14, and 21 have all been implicated in the pathogenesis of the early-onset form of the disease, while the epsilon 4 allele of the apolipoprotein E gene (on chromosome 19) is now recognized as a risk factor for early- and late-onset sporadic and familial Alzheimer's disease. 2. The best-established environmental trigger for the disease is a head injury, based on epidemiological and neuropathological evidence. Approximately 30% of patients who die after a single episode of severe head injury show intracerebral deposition of beta-amyloid protein (A beta), a protein that is thought to be central to the pathogenesis of Alzheimer's disease. 3. Recent studies have revealed an over-representation of the apoE epsilon 4 allele in those head-injured patients displaying A beta pathology, thus providing the first evidence for a link between a genetic susceptibility (apoE epsilon 4) and an environmental trigger (head injury) in the development of Alzheimer-type pathology.
摘要
  1. 阿尔茨海默病是一种异质性疾病,可能由遗传因素、环境因素或两者共同作用引起。1号、14号和21号染色体异常均与早发型阿尔茨海默病的发病机制有关,而载脂蛋白E基因(位于19号染色体)的ε4等位基因现已被确认为早发型和晚发型散发性及家族性阿尔茨海默病的一个风险因素。2. 根据流行病学和神经病理学证据,该疾病最明确的环境触发因素是头部损伤。在单次严重头部损伤后死亡的患者中,约30%的患者脑内出现β-淀粉样蛋白(Aβ)沉积,这种蛋白被认为是阿尔茨海默病发病机制的核心。3. 最近的研究表明,在那些表现出Aβ病理特征的头部受伤患者中,载脂蛋白Eε4等位基因的比例过高,从而首次证明了在阿尔茨海默病型病理发展过程中,遗传易感性(载脂蛋白Eε4)与环境触发因素(头部损伤)之间存在联系。

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