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阿尔茨海默病中的基底膜与β淀粉样蛋白纤维形成

Basement membrane and beta amyloid fibrillogenesis in Alzheimer's disease.

作者信息

Inoue S

机构信息

Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.

出版信息

Int Rev Cytol. 2001;210:121-61. doi: 10.1016/s0074-7696(01)10005-7.

DOI:10.1016/s0074-7696(01)10005-7
PMID:11580205
Abstract

High-resolution ultrastructural and immunohistochemical studies revealed that in situ beta amyloid fibrils of Alzheimer's disease were made up of a core consisting of a solid column of amyloid P component (AP) and associated chondroitin sulfate proteoglycan, and a heparan sulfate proteoglycan surface layer with externally associated fine filaments of beta protein. The main body of beta amyloid fibrils closely resembled that of microfibrils. Abundant microfibrils were reported to be present at the basement membrane of capillaries with "leaky" blood-urine or blood-air barriers. Similarly, abundant microfibril-like beta amyloid fibrils are formed at the microvascular basement membrane in cerebrovascular amyloid angiopathy with altered blood-brain barrier. Since AP is an indispensable major component of microfibrils and microfibril-like structures, the formation of microfibrils may depend on, among other factors, the availability of AP. Thus, in beta amyloid fibrillogenesis fibrils may be built around AP which continuously leaks out from circulation into vascular basement membrane, and beta amyloid fibrils may be regarded as pathologically altered basement membrane-associated microfibrils. With no source of AP around them, senile plaque fibrils may also be derived from perivascular amyloid.

摘要

高分辨率超微结构和免疫组织化学研究表明,阿尔茨海默病的原位β淀粉样蛋白纤维由一个核心组成,该核心由淀粉样蛋白P成分(AP)的实心柱和相关的硫酸软骨素蛋白聚糖构成,以及一个硫酸乙酰肝素蛋白聚糖表面层,其外部伴有β蛋白的细丝。β淀粉样蛋白纤维的主体与微纤维非常相似。据报道,在具有“渗漏”血尿或血气屏障的毛细血管基底膜处存在大量微纤维。同样,在血脑屏障改变的脑血管淀粉样血管病的微血管基底膜处形成大量微纤维样β淀粉样蛋白纤维。由于AP是微纤维和微纤维样结构不可或缺的主要成分,微纤维的形成可能除其他因素外还取决于AP的可用性。因此,在β淀粉样蛋白纤维形成过程中,纤维可能围绕从循环中持续渗漏到血管基底膜的AP构建,并且β淀粉样蛋白纤维可被视为病理改变的基底膜相关微纤维。由于周围没有AP来源,老年斑纤维也可能源自血管周围淀粉样蛋白。

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