Sensitive quantitative assays for tau and phospho-tau in transgenic mouse models

Sensitive quantitative assays for tau and phospho-tau in transgenic mouse models
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DOI:
10.1016/j.neurobiolaging.2012.05.010
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发表时间:
2013-01-01
影响因子:
4.2
通讯作者:
d'Abramo, Cristina
d'Abramo, Cristina
中科院分区:
医学2区
文献类型:
--
作者:
Acker, Christopher M.;Forest, Stefanie K.;d'Abramo, Cristina

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转基因小鼠模型是阐明β-淀粉样蛋白和tau蛋白在阿尔茨海默病中复杂作用的宝贵资源。尽管许多实验室在研究tau病理学时依赖于定性或半定量技术,但我们已经开发了4种Low-Tau夹心酶联免疫吸附试验(ELISA),可定量评估与阿尔茨海默病相关的tau的不同表位:总tau,pSer-202,pThr-231和pSer-396/404。在这项研究中,在比较我们的测定与市售ELISA,我们证明了我们的测定的高特异性和定量能力,使用脑匀浆从tau转基因小鼠,htau,JNPL 3,和tau敲除。所有4种ELISA均显示出对小鼠和人tau的优异特异性,对tau敲除动物无反应性。在两种tau转基因模型中也观察到血清tau的年龄依赖性增加。总之,这些测定是通过检查脑中的tau水平和测量作为潜在血清生物标志物的tau来定量转基因动物中的tau和磷酸化tau水平的有价值的方法。(C)2013 Elsevier Inc. All rights reserved.
Transgenic mouse models have been an invaluable resource in elucidating the complex roles of beta-amyloid and tau in Alzheimer's disease. Although many laboratories rely on qualitative or semiquantitative techniques when investigating tau pathology, we have developed 4 Low-Tau, Sandwich enzyme-linked immunosorbent assays (ELISAs) that quantitatively assess different epitopes of tau relevant to Alzheimer's disease: total tau, pSer-202, pThr-231, and pSer-396/404. In this study, after comparing our assays with commercially available ELISAs, we demonstrate our assay's high specificity and quantitative capabilities using brain homogenates from tau transgenic mice, htau, JNPL3, and tau knockout. All 4 ELISAs show excellent specificity for mouse and human tau, with no reactivity to tau knockout animals. An age-dependent increase of serum tau in both tau transgenic models was also seen. Taken together, these assays are valuable methods to quantify tau and phospho-tau levels in transgenic animals, by examining tau levels in brain and measuring tau as a potential serum biomarker. (C) 2013 Elsevier Inc. All rights reserved.