Caspase-Cleaved Tau Co-Localizes with Early Tangle Markers in the Human Vascular Dementia Brain.
Caspase-Cleaved Tau Co-Localizes with Early Tangle Markers in the Human Vascular Dementia Brain.
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DOI：
10.1371/journal.pone.0132637
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Rohn TT
中科院分区：
文献类型：
--
作者：
Day RJ;Mason MJ;Thomas C;Poon WW;Rohn TT
血管性痴呆（VaD）是美国第二常见的痴呆形式，其特征在于导致缺血发作的脑血管疾病。尽管先前已经描述了阿尔茨海默病（AD）中半胱天冬酶切割的tau蛋白和神经元缠结（NFT）之间的关系，但VaD中是否发生半胱天冬酶活化和tau蛋白切割目前尚不清楚。为了研究半胱天冬酶切割的tau蛋白在VaD中的潜在作用，我们通过免疫组织化学分析了7例确诊的VaD病例，该免疫组织化学利用了一种充分表征的抗体，该抗体特异性检测Asp 421截短的半胱天冬酶切割的tau蛋白。该抗体（TauC 3）的应用揭示了人VaD脑中NFT、斑块富集区域内的营养不良性神经突和淀粉体（CA）内的一致标记。CA的TauC 3抗体的标记是广泛的整个海马体适当的，是显着高于年龄匹配的对照组，并与泛素共定位。TauC 3抗体的染色与MC-1、AT 8和PHF-1共定位在NFT内。定量分析表明，大约90%的PHF-1标记的NFT含有半胱天冬酶切割的tau蛋白。此外，我们记录了与TauC 3共定位的斑块、血管和预缠结神经元内活性胱天蛋白酶-3的存在。总的来说，这些数据支持半胱天冬酶-3的活化和TauC 3的蛋白水解裂解在VaD中的作用，进一步支持该蛋白酶家族参与NFT病理学。
Vascular dementia (VaD) is the second most common form of dementia in the United States and is characterized as a cerebral vessel vascular disease that leads to ischemic episodes. Whereas the relationship between caspase-cleaved tau and neurofibrillary tangles (NFTs) in Alzheimer’s disease (AD) has been previously described, whether caspase activation and cleavage of tau occurs in VaD is presently unknown. To investigate a potential role for caspase-cleaved tau in VaD, we analyzed seven confirmed cases of VaD by immunohistochemistry utilizing a well-characterized antibody that specifically detects caspase-cleaved tau truncated at Asp421. Application of this antibody (TauC3) revealed consistent labeling within NFTs, dystrophic neurites within plaque-rich regions and corpora amylacea (CA) in the human VaD brain. Labeling of CA by the TauC3 antibody was widespread throughout the hippocampus proper, was significantly higher compared to age matched controls, and co-localized with ubiquitin. Staining of the TauC3 antibody co-localized with MC-1, AT8, and PHF-1 within NFTs. Quantitative analysis indicated that roughly 90% of PHF-1-labeled NFTs contained caspase-cleaved tau. In addition, we documented the presence of active caspase-3 within plaques, blood vessels and pretangle neurons that co-localized with TauC3. Collectively, these data support a role for the activation of caspase-3 and proteolytic cleavage of TauC3 in VaD providing further support for the involvement of this family of proteases in NFT pathology.
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DOI：
10.1073/pnas.121119298
发表时间：
2001-06-05
影响因子：
11.1
作者：
Alonso, AD;Zaidi, T;Iqbal, K
通讯作者：
Iqbal, K
影响因子：
2.5
作者：
GOEDERT, M;JAKES, R;VANMECHELEN, E
通讯作者：
VANMECHELEN, E
DOI：
10.1073/pnas.1630428100
发表时间：
2003-08-19
影响因子：
11.1
作者：
Gamblin, TC;Chen, F;Cryns, VL
通讯作者：
Cryns, VL
影响因子：
7.2
作者：
Rohn, Troy T.
通讯作者：
Rohn, Troy T.
影响因子：
15.9
作者：
Rissman, RA;Poon, WW;Cotman, CW
通讯作者：
Cotman, CW