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硫酸乙酰肝素蛋白聚糖在阿尔茨海默病的神经炎性斑块和嗜刚果红血管病变中的存在。

The presence of heparan sulfate proteoglycans in the neuritic plaques and congophilic angiopathy in Alzheimer's disease.

作者信息

Snow A D, Mar H, Nochlin D, Kimata K, Kato M, Suzuki S, Hassell J, Wight T N

机构信息

Department of Pathology, University of Washington, Seattle 98195.

出版信息

Am J Pathol. 1988 Dec;133(3):456-63.

PMID:2974240
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1880818/
Abstract

Two immunocytochemical probes were used to specifically identify and localize heparan sulphate proteoglycans (HSPGs) in 17 cases of Alzheimer's disease (AD). A monoclonal (HK-102) and an affinity-purified polyclonal antibody, each recognizing specific domains on the protein core of a basement membrane-derived HSPG, localized HSPGs to the amyloid fibrils present in neuritic plaques (NPs) and congophilic angiopathy (CA) in the brains of Alzheimer's patients, with weak to no immunostaining in neurofibrillary tangles from the same tissues. HSPGs were also demonstrated in "primitive plaques," suggesting that their accumulation takes place during early stages of plaque development. Immunolocalization of HSPGs to subsets of astrocytes and neuronal cells, particularly those in close proximity to NPs and CA, suggested possible involvement of these two cell types in deposition of HS-PGs into the amyloidotic lesions. The current study not only identifies a new component (HSPGs) present in the amyloid deposits of NPs and CA but also suggests that astrocytes, neurons, or both may be involved in its deposition at these sites.

摘要

使用两种免疫细胞化学探针,特异性鉴定并定位17例阿尔茨海默病(AD)患者脑中的硫酸乙酰肝素蛋白聚糖(HSPG)。一种单克隆抗体(HK-102)和一种亲和纯化的多克隆抗体,各自识别源自基底膜的HSPG蛋白核心上的特定结构域,将HSPG定位到阿尔茨海默病患者脑中神经炎性斑块(NP)和嗜刚果红血管病(CA)中存在的淀粉样纤维上,而相同组织的神经原纤维缠结中免疫染色较弱或无染色。在“原始斑块”中也证实了HSPG的存在,这表明它们在斑块形成的早期阶段就开始积累。HSPG在星形胶质细胞和神经元细胞亚群中的免疫定位,特别是那些紧邻NP和CA的细胞,提示这两种细胞类型可能参与了HS-PG在淀粉样病变中的沉积。当前研究不仅鉴定出NP和CA淀粉样沉积物中存在的一种新成分(HSPG),还表明星形胶质细胞、神经元或两者可能参与了其在这些部位的沉积。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bf4/1880818/65a737a18c17/amjpathol00129-0043-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bf4/1880818/d906e83c69bf/amjpathol00129-0041-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bf4/1880818/65a737a18c17/amjpathol00129-0043-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bf4/1880818/d906e83c69bf/amjpathol00129-0041-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bf4/1880818/65a737a18c17/amjpathol00129-0043-a.jpg

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本文引用的文献

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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
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Multi-omic analysis of meningeal cerebral amyloid angiopathy reveals enrichment of unsubstituted glucosamine and extracellular proteins.脑膜脑淀粉样血管病的多组学分析揭示了未取代氨基葡萄糖和细胞外蛋白的富集。
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Paired helical filaments from Alzheimer disease patients contain cytoskeletal components.来自阿尔茨海默病患者的成对螺旋丝含有细胞骨架成分。
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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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An immunohistochemical quantification of fibrous astrocytes in the aging human cerebral cortex.
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The role of endogenous heparan sulfate proteoglycan in adhesion and neurite outgrowth from dorsal root ganglia.内源性硫酸乙酰肝素蛋白聚糖在背根神经节黏附及神经突生长中的作用
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