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小牛血清中存在一种能识别福尔马林固定切片中β淀粉样蛋白的新型蛋白质。

The presence of a novel protein in calf serum that recognizes beta amyloid in the formalin-fixed section.

作者信息

Kanemaru K, Hasegawa M, Shimada H, Ihara Y

机构信息

Second Laboratory of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Japan.

出版信息

Am J Pathol. 1990 Sep;137(3):677-87.

PMID:1698030
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1877531/
Abstract

Here we report on a monoclonal antibody, H6-33, that labels various beta-amyloid plaques, including diffuse plaques in the formalin-fixed, paraffin-embedded section from the brain affected with Alzheimer's disease (AD), without formic acid pretreatment. H6-33 also labels some neurofibrillary tangles and all kuru plaques in Gerstmann-Sträussler-Scheinker disease. In sharp contrast, H6-33 did not stain beta amyloid in the leptomeningeal vessel. For specific staining, H6-33 required the presence of fetal calf serum and it was necessary for beta amyloid to be formalin fixed. These results suggest that a novel protein in the calf serum, CSX, binds formalin-fixed beta amyloid, followed by H6-33 binding. The detection of beta amyloid by CSX was nullified by formic acid pretreatment of the tissue section. In accordance with this, CSX reacted only with a polymer form of synthetic beta peptide after fixation, but not with native beta-protein or beta-peptide monomer. These observations strongly suggest that 1) meningovascular beta amyloid should have a beta-pleated sheet structure somewhat dissimilar to that of beta-amyloid cores; and 2) most, if not all, of beta-protein immunoreactivities of diffuse plaques in AD sections are presumably derived from small amounts of amyloid fibrils scattered in the normal-looking neurohil.

摘要

在此,我们报告一种单克隆抗体H6 - 33,它可标记各种β淀粉样斑块,包括来自阿尔茨海默病(AD)患者大脑的福尔马林固定石蜡包埋切片中的弥漫性斑块,无需甲酸预处理。H6 - 33还可标记格斯特曼 - 施特劳斯勒 - 申克病中的一些神经原纤维缠结和所有库鲁斑块。形成鲜明对比的是,H6 - 33未对软脑膜血管中的β淀粉样蛋白进行染色。为进行特异性染色,H6 - 33需要胎牛血清的存在,且β淀粉样蛋白需经福尔马林固定。这些结果表明,胎牛血清中的一种新蛋白CSX可结合福尔马林固定的β淀粉样蛋白,随后H6 - 33与之结合。组织切片经甲酸预处理后,CSX对β淀粉样蛋白的检测无效。据此,CSX仅在固定后与合成β肽的聚合物形式发生反应,而不与天然β蛋白或β肽单体发生反应。这些观察结果强烈表明:1)脑膜血管β淀粉样蛋白应具有与β淀粉样核心有些不同的β折叠结构;2)AD切片中弥漫性斑块的大部分(如果不是全部)β蛋白免疫反应性可能源自散在于看似正常的神经纤维网中的少量淀粉样纤维。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc08/1877531/87aef61d5b86/amjpathol00105-0197-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc08/1877531/85ddbaec8e75/amjpathol00105-0193-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc08/1877531/8852885f454f/amjpathol00105-0194-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc08/1877531/7ac4e5cfb2bc/amjpathol00105-0195-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc08/1877531/c1ede60e8379/amjpathol00105-0196-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc08/1877531/87aef61d5b86/amjpathol00105-0197-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc08/1877531/85ddbaec8e75/amjpathol00105-0193-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc08/1877531/8852885f454f/amjpathol00105-0194-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc08/1877531/7ac4e5cfb2bc/amjpathol00105-0195-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc08/1877531/c1ede60e8379/amjpathol00105-0196-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc08/1877531/87aef61d5b86/amjpathol00105-0197-a.jpg

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引用本文的文献

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本文引用的文献

1
In vitro immunization as an adjunct to the production of hybridomas producing antibodies against the lymphokine osteoclast activating factor.体外免疫作为生产抗淋巴因子破骨细胞激活因子抗体的杂交瘤的辅助手段。
Mol Immunol. 1980 May;17(5):635-9. doi: 10.1016/0161-5890(80)90161-3.
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Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein.阿尔茨海默病:一种新型脑血管淀粉样蛋白的纯化与特性的初步报告
Biochem Biophys Res Commun. 1984 May 16;120(3):885-90. doi: 10.1016/s0006-291x(84)80190-4.
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Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels.
大脑淀粉样蛋白的神经元起源:阿尔茨海默病的神经原纤维缠结与斑块核心及血管淀粉样蛋白含有相同蛋白质。
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Serum albumin.血清白蛋白
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Formaldehyde fixation.甲醛固定
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Sulfated glycosaminoglycans in Alzheimer's disease.阿尔茨海默病中的硫酸化糖胺聚糖
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In vitro formation of amyloid fibrils from two synthetic peptides of different lengths homologous to Alzheimer's disease beta-protein.由与阿尔茨海默病β蛋白同源的两种不同长度的合成肽在体外形成淀粉样原纤维。
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Isolation of low-molecular-weight proteins from amyloid plaque fibers in Alzheimer's disease.从阿尔茨海默病淀粉样斑块纤维中分离低分子量蛋白质。
J Neurochem. 1986 Jun;46(6):1820-34. doi: 10.1111/j.1471-4159.1986.tb08501.x.
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Synthetic peptide homologous to beta protein from Alzheimer disease forms amyloid-like fibrils in vitro.与阿尔茨海默病β蛋白同源的合成肽在体外形成淀粉样原纤维。
Proc Natl Acad Sci U S A. 1987 Oct;84(19):6953-7. doi: 10.1073/pnas.84.19.6953.
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Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease.荷兰裔患者的遗传性淀粉样变性脑出血与阿尔茨海默病有关。
Proc Natl Acad Sci U S A. 1987 Aug;84(16):5991-4. doi: 10.1073/pnas.84.16.5991.