Apolipoprotein E pathology in vascular dementia.
Apolipoprotein E pathology in vascular dementia.
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发表时间：
2014-02
影响因子：
1.4
通讯作者：
T. Rohn;R. Day;Colin B Sheffield;Alexander J. Rajic;W. Poon
中科院分区：
文献类型：
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作者：
T. Rohn;R. Day;Colin B Sheffield;Alexander J. Rajic;W. Poon
血管性痴呆（VaD）是第二种最常见的痴呆形式，目前被定义为导致缺血发作的脑血管疾病。载脂蛋白E（apoE）基因多态性已被认为是VaD的一个危险因素，然而，迄今为止，关于VaD脑内apoE病理学的尸检研究很少。为了研究apoE蛋白的潜在作用，我们分析了7例确诊的VaD的免疫组化利用抗体，特异性检测apoE的氨基末端片段。这种抗体的应用，称为N-末端，apoE裂解片段（nApoECF）揭示了一致的标记内神经元缠结（NFT），血管，和反应性星形胶质细胞。标记发生在VaD的情况下，已确认APOE基因型为3/3，3/4和4/4，就NFT而言，nApoECF的染色与PHF-1共定位，并主要定位于内嗅皮质第II层中的大型星状神经元。定量分析表明，约38.4%的所有鉴定的NFT含有apoE的氨基端片段。总的来说，这些数据支持了在VaD中apoE的蛋白水解裂解的作用，并支持先前的报道，即APOE多态性与这种疾病的易感性显著相关。
Vascular dementia (VaD) is the second most common form of dementia and is currently defined as a cerebral vessel vascular disease leading to ischemic episodes. Apolipoprotein E (apoE) gene polymorphism has been proposed as a risk factor for VaD, however, to date there are few documented post-mortem studies on apoE pathology in the VaD brain. To investigate a potential role for the apoE protein, we analyzed seven confirmed cases of VaD by immunohistochemistry utilizing an antibody that specifically detects the amino-terminal fragment of apoE. Application of this antibody, termed N-terminal, apoE cleavage fragment (nApoECF) revealed consistent labeling within neurofibrillary tangles (NFTs), blood vessels, and reactive astrocytes. Labeling occurred in VaD cases that had confirmed APOE genotypes of 3/3, 3/4, and 4/4, with respect to NFTs, staining of the nApoECF co-localized with PHF-1 and was predominantly localized to large, stellate neurons in layer II of the entorhinal cortex. Quantitative analysis indicated that approximately 38.4% of all identified NFTs contained the amino-terminal fragment of apoE. Collectively, these data support a role for the proteolytic cleavage of apoE in the VaD and support previous reports that APOE polymorphism is significantly associated with susceptibility in this disease.