Immunolocalization of an amino-terminal fragment of apolipoprotein E in the Pick's disease brain.

Immunolocalization of an amino-terminal fragment of apolipoprotein E in the Pick's disease brain.
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DOI:
10.1371/journal.pone.0080180
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Poon WW
Poon WW
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Rohn TT;Day RJ;Catlin LW;Brown RJ;Rajic AJ;Poon WW

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尽管载脂蛋白E (apoE)多态性在阿尔茨海默病(AD)中的风险因素已被很好地描述,但载脂蛋白E在包括匹克病在内的其他神经退行性疾病中的作用尚未得到很好的确定。为了研究载脂蛋白e在匹克病中的可能作用,利用一种新的位点定向抗体进行了免疫组织化学分析,该抗体对载脂蛋白e的氨基末端片段具有特异性。该抗体被称为氨基端apoE切割片段(nApoECF)抗体,在5例检测的病例中,有4例在海马CA1区一致标记Pick小体。nApoECF抗体与PHF-1 (Pick小体的一般标记物)以及针对caspase-cleaved tau (TauC3)的抗体在海马体内的共定位很明显。虽然naapoecf抗体在CA1区染色牢固,但在齿状回内的Pick小体中几乎没有观察到与PHF-1共定位。定量分析表明,在CA1区鉴定的Pick小体中,约有86%标记有nApoECF抗体。匹克病体内截短的载脂蛋白e的存在表明载脂蛋白e在AD之外具有更广泛的作用,并提出了该蛋白是否与匹克病相关的发病机制有关的问题。
Although the risk factor for apolipoprotein E (apoE) polymorphism in Alzheimer's disease (AD) has been well described, the role that apoE plays in other neurodegenerative diseases, including Pick's disease, is not well established. To examine a possible role of apoE in Pick's disease, an immunohistochemical analysis was performed utilizing a novel site-directed antibody that is specific for an amino-terminal fragment of apoE. Application of this antibody, termed the amino-terminal apoE cleavage fragment (nApoECF) antibody, consistently labeled Pick bodies within area CA1 of the hippocampus in 4 of the 5 cases examined. Co-localization of the nApoECF antibody with PHF-1, a general marker for Pick bodies, as well as with an antibody to caspase-cleaved tau (TauC3) was evident within the hippocampus. While staining of the nApoECF antibody was robust in area CA1, little co-localization with PHF-1 in Pick bodies within the dentate gyrus was observed. A quantitative analysis indicated that approximately 86% of the Pick bodies identified in area CA1 labeled with the nApoECF antibody. The presence of truncated apoE within Pick bodies suggests a broader role of apoE beyond AD and raises the question as to whether this protein contributes to pathogenesis associated with Pick's disease.
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