Isolation and characterization of antibody fragments selective for toxic oligomeric tau.
Isolation and characterization of antibody fragments selective for toxic oligomeric tau.
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DOI：
10.1016/j.neurobiolaging.2014.12.002
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发表时间：
2015-03
影响因子：
4.2
通讯作者：
Sierks MR
中科院分区：
文献类型：
--
作者：
Tian H;Davidowitz E;Lopez P;He P;Schulz P;Moe J;Sierks MR
寡聚体tau在阿尔茨海默病(AD)的发生和发展中起重要作用，因为它们具有神经毒性，并能传播tau缠结的病理。因此，需要选择性地识别不同关键形态的tau的试剂来帮助确定tau在AD和相关疾病中的作用。我们利用一种生物扫描方法，结合噬菌体展示抗体库的结合多样性和原子力显微镜(AFM)的强大成像能力来分离选择性结合有毒寡聚体tau的单链抗体片段(ScFv)。我们分离了三个不同的抗体片段，它们结合的是寡聚体，而不是单体或纤维状tau。单链抗体将3×TG和tau-AD小鼠的脑组织匀浆与野生型小鼠区分开来，检测到寡聚tau的年龄比通常检测到神经原纤维缠结的年龄要早得多。单链抗体还可以区分人类死后AD脑组织和认知正常的死后人类脑组织，展示了这种方法开发用于AD早期检测和进展的生物标志物的潜力。
Oligomeric tau species are important in the onset and progression of Alzheimer’s Disease (AD) as they are neurotoxic and can propagate tau tangle pathology. Therefore reagents that selectively recognize different key morphologies of tau are needed to help define the role of tau in AD and related diseases. We utilized a biopanning protocol that combines the binding diversity of phage-displayed antibody libraries with the powerful imaging capability of atomic force microscopy (AFM) to isolate single chain antibody fragments (scFvs) that selectively bind toxic oligomeric tau. We isolated three different antibody fragments that bind oligomeric but not monomeric or fibrillar tau. The scFvs differentiate brain tissue homogenates of both 3×TG and tau-AD mice from wild type mice, detecting oligomeric tau at much earlier ages than when neurofibrillary tangles are typically detected. The scFvs also distinguish human post-mortem AD brain tissue from cognitively normal post-mortem human brain tissue demonstrating the potential of this approach for developing biomarkers for early detection and progression of AD.
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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：
14
作者：
通讯作者：
--
影响因子：
4
作者：
Castillo-Carranza, Diana L.;Gerson, Julia E.;Kayed, Rakez
通讯作者：
Kayed, Rakez
影响因子：
2.4
作者：
Barkhordarian, Hedieh;Emadi, Sharareh;Sierks, Michael R.
通讯作者：
Sierks, Michael R.
影响因子：
16.8
作者：
Cohen TJ;Friedmann D;Hwang AW;Marmorstein R;Lee VM
通讯作者：
Lee VM