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[老年斑淀粉样蛋白中80 kDa抗原的分析]

[Analysis of the 80 kDa antigen in senile plaque amyloid].

作者信息

Takamaru Y

机构信息

Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo, Japan.

出版信息

Hokkaido Igaku Zasshi. 1994 Mar;69(2):191-201.

PMID:8157246
Abstract

Amyloid deposition is the major hallmark of Alzheimer's disease (AD). Beta/A4 protein is identified as the major component of amyloid in the brains of AD. But all the components of amyloid and the precise mechanism of amyloid formation are still unknown. To provide better understanding of amyloidogenesis in AD brain, we have established 12 monoclonal antibodies (mcAb's) which immunohistochemically reacted with amyloid or amyloid-related structures, and tried to characterize these mcAb's. The epitopes, which these mcAb's reacted with, have been studied, and 2 of these mcAb's (Az 172/4, Az 520/4) turned out to react with protein of 80 kDa in brain homogenate or normal human plasma (NHP). Reactive antigen was purified from NHP using PEG fractionation, and immunoaffinity column. Amino-terminus amino acid sequence analysis of purified antigen was performed, and the results showed that 80 kDa antigen was identical to SP-40, 40 (or clusterin). Immunohistochemical study revealed that various types of senile plaque and vascular amyloid were stained with the mcAb's. In addition, fibrous background structures were also stained in AD brain. But there were no positive structures in control brains. The above observations indicate that SP-40, 40 is expressed and deposited in AD brain. This protein is closely associated with amyloid deposition. SP-40, 40 seems to play an important role in pathogenesis of amyloid formation in AD.

摘要

淀粉样蛋白沉积是阿尔茨海默病(AD)的主要标志。β/A4蛋白被确定为AD患者大脑中淀粉样蛋白的主要成分。但淀粉样蛋白的所有成分以及淀粉样蛋白形成的确切机制仍不清楚。为了更好地理解AD大脑中的淀粉样蛋白生成过程,我们制备了12种单克隆抗体(mcAb),这些抗体与淀粉样蛋白或淀粉样蛋白相关结构发生免疫组织化学反应,并试图对这些mcAb进行特性分析。已经研究了这些mcAb所反应的表位,结果发现其中2种mcAb(Az 172/4、Az 520/4)能与脑匀浆或正常人血浆(NHP)中的80 kDa蛋白发生反应。使用聚乙二醇分级分离和免疫亲和柱从NHP中纯化反应性抗原。对纯化抗原进行了氨基末端氨基酸序列分析,结果表明80 kDa抗原与SP-40、40(或簇集蛋白)相同。免疫组织化学研究显示,各种类型的老年斑和血管淀粉样蛋白都被这些mcAb染色。此外,AD大脑中的纤维状背景结构也被染色。但对照大脑中没有阳性结构。上述观察结果表明,SP-40、40在AD大脑中表达并沉积。这种蛋白与淀粉样蛋白沉积密切相关。SP-40、40似乎在AD淀粉样蛋白形成的发病机制中起重要作用。

相似文献

1
[Analysis of the 80 kDa antigen in senile plaque amyloid].[老年斑淀粉样蛋白中80 kDa抗原的分析]
Hokkaido Igaku Zasshi. 1994 Mar;69(2):191-201.
2
Clusterin (apolipoprotein J) protein levels are increased in hippocampus and in frontal cortex in Alzheimer's disease.在阿尔茨海默病患者的海马体和额叶皮质中,聚集素(载脂蛋白J)的蛋白水平会升高。
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4
CLAC: a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC-P/collagen type XXV.CLAC:一种源自跨膜前体CLAC-P/XXV型胶原蛋白的新型阿尔茨海默病淀粉样斑块成分。
EMBO J. 2002 Apr 2;21(7):1524-34. doi: 10.1093/emboj/21.7.1524.
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Immunoaffinity chromatographic purification of amyloid-related proteins from Alzheimer's disease brain tissue.
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High sensitivity analysis of amyloid-beta peptide composition in amyloid deposits from human and PS2APP mouse brain.人源和PS2APP小鼠脑内淀粉样沉积物中β淀粉样肽组成的高灵敏度分析
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Amyloid beta protein starting pyroglutamate at position 3 is a major component of the amyloid deposits in the Alzheimer's disease brain.在第3位起始于焦谷氨酸的β淀粉样蛋白是阿尔茨海默病大脑中淀粉样沉积物的主要成分。
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Neuropathological characterization of mutant amyloid precursor protein yeast artificial chromosome transgenic mice.突变淀粉样前体蛋白酵母人工染色体转基因小鼠的神经病理学特征
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RAGE, LRP-1, and amyloid-beta protein in Alzheimer's disease.阿尔茨海默病中的晚期糖基化终末产物受体、低密度脂蛋白受体相关蛋白1及β-淀粉样蛋白
Acta Neuropathol. 2006 Oct;112(4):405-15. doi: 10.1007/s00401-006-0115-3. Epub 2006 Jul 25.
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Alzheimer's disease--a spirochetosis?阿尔茨海默病——一种螺旋体病?
Neuroreport. 1993 Jul;4(7):841-8.

引用本文的文献

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The genetic architecture of Alzheimer's disease: beyond APP, PSENs and APOE.阿尔茨海默病的遗传结构:超越 APP、PSENs 和 APOE。
Neurobiol Aging. 2012 Mar;33(3):437-56. doi: 10.1016/j.neurobiolaging.2010.03.025. Epub 2010 Jul 1.
2
Genetic variability in CLU and its association with Alzheimer's disease.CLU 基因的遗传多态性及其与阿尔茨海默病的关联。
PLoS One. 2010 Mar 3;5(3):e9510. doi: 10.1371/journal.pone.0009510.