Glenner G G
University of California, San Diego, Department of Pathology, School of Medicine, La Jolla 92093.
Prog Clin Biol Res. 1989;317:857-68.
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.
从脑血管淀粉样沉积物中分离出的淀粉样纤维蛋白，在92%的阿尔茨海默病病例和100% 40岁以上的唐氏综合征病例中可见，已被证明具有先前未知的氨基酸序列。这种蛋白质被命名为β蛋白（βP），淀粉样纤维类型为ACvβ。针对包含βP前10个氨基酸的合成肽产生的多克隆和单克隆抗体，既能定位到脑血管淀粉样沉积物，也能定位到所有“老年”斑的淀粉样核心。据报道，基于βP的氨基酸序列分析表明，斑淀粉样纤维沉积物也由βP组成。这些沉积物必定会严重破坏神经纤维。因此，淀粉样沉积物形式的βP似乎是神经元功能破坏以及随之而来的阿尔茨海默病痴呆症的内在因素。由于蛋白水解作用将βP前体（PreβP）转化为淀粉样纤维，有可能：1）PreβP合成异常，可能发生在翻译后事件期间；或者2）蛋白水解加工异常，从而导致βP沉积和阿尔茨海默病的病理变化。无论加工异常情况如何，βP都是阿尔茨海默病发病机制中的主要成分。
