Amyloid beta protein and the basis for Alzheimer's disease.
Amyloid beta protein and the basis for Alzheimer's disease.
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发表时间：
1989
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通讯作者：
G. Glenner
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作者：
G. Glenner
从92%的阿尔茨海默病患者和100%40岁以上的唐氏综合症患者的脑血管淀粉样沉积中分离出的淀粉样纤维蛋白被证明具有以前未知的氨基酸序列。这种蛋白被命名为β蛋白(βP)和淀粉样蛋白纤维类型，ACVβ。多克隆和单克隆抗体被提升为含有βP的前10个氨基酸的合成肽，定位于脑血管淀粉样沉积以及所有“老年”斑块的淀粉样核。据报道，基于βP的氨基酸序列分析表明，斑块中的淀粉样纤维沉积也是由βP组成的，这些沉积一定会导致神经纤维的严重破坏。因此，淀粉样蛋白沉积形式的βP似乎是神经元功能破坏的内在原因，从而导致阿尔茨海默病的痴呆症。由于蛋白分解会将βP前体(前βP)转化为淀粉样纤维，因此有可能1)前βP合成异常，可能是在过渡后事件中，或2)蛋白分解过程中发生异常，以提供βP沉积和阿尔茨海默病的病理变化。无论加工异常如何，βP都是阿尔茨海默病发病机制中的一个重要组成部分。
The amyloid fibril protein isolated from the cerebrovascular amyloid deposits seen in 92% of cases of Alzheimer's disease and 100% of cases of Down's syndrome over the age of 40 has been shown to have a previously unknown amino acid sequence. This protein has been designated beta protein (beta P) and the type amyloid fibrils, ACv beta. Polyclonal and monoclonal antibodies raised to a synthetic peptide comprising the first 10 amino acids of beta P localized both to cerebrovascular amyloid deposits as well as to the amyloid cores of all "senile" plaques. An amino acid sequence analysis based on that of the beta P has been reported indicating that the plaque amyloid fibril deposits are also composed of beta P. These deposits must cause severe disruption of neuronal fibers. Thus beta P in the form of amyloid deposits seems intrinsic to the destruction of neuronal competence and thus to the ensuing dementia of Alzheimer's disease. Since proteolysis converts the beta P precursor (Pre beta P) into amyloid fibrils, it is possible that 1) an abnormality in synthesis of the Pre beta P, perhaps during post-transitional events, or 2) an abnormality in proteolytic processing occurs to afford beta P deposits and the pathologic changes in Alzheimer's disease. Regardless of the processing abnormality, beta P represents a major component in the pathogenesis of Alzheimer's disease.