Generation and characterization of new monoclonal antibodies targeting the PHF1 and AT8 epitopes on human tau.
Generation and characterization of new monoclonal antibodies targeting the PHF1 and AT8 epitopes on human tau.
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DOI：
10.1186/s40478-017-0458-0
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发表时间：
2017-07-31
影响因子：
7.1
通讯作者：
Giasson BI
中科院分区：
文献类型：
--
作者：
Strang KH;Goodwin MS;Riffe C;Moore BD;Chakrabarty P;Levites Y;Golde TE;Giasson BI
tau蛋白病是一组神经退行性疾病，包括阿尔茨海默病，其定义为存在由异常聚集和高度磷酸化的tau蛋白组成的脑病理性包涵体。脑tau聚集体的丰度与疾病的严重程度相关，并且选择的磷酸化tau表位在疾病的早期阶段增加。我们产生并表征了一系列针对tau蛋白磷酸化的新型单克隆抗体，这些磷酸化表位包括Ser 396/Ser 404、Ser 404和Thr 205。我们还产生了针对氨基酸残基193-211的磷酸化非依赖性抗体。我们表明，这些抗体中的大多数是高度特异性的tau蛋白，并强烈识别人类大脑中的病理性夹杂物和在转基因小鼠模型的tau蛋白病。它们还揭示了阿尔茨海默病肌酰不溶性tau蛋白生物化学性质的表位特异性差异。这些新试剂将有助于研究tau病理学的进展，并进一步作为靶向tau病理学细胞传播的工具。
Tauopathies are a group of neurodegenerative disorders, including Alzheimer’s disease, defined by the presence of brain pathological inclusions comprised of abnormally aggregated and highly phosphorylated tau protein. The abundance of brain tau aggregates correlates with disease severity and select phospho-tau epitopes increase at early stages of disease. We generated and characterized a series of novel monoclonal antibodies directed to tau phosphorylated at several of these phospho-epitopes, including Ser396/Ser404, Ser404 and Thr205. We also generated phosphorylation independent antibodies against amino acid residues 193–211. We show that most of these antibodies are highly specific for tau and strongly recognize pathological inclusions in human brains and in a transgenic mouse model of tauopathy. They also reveal epitope-specific differences in the biochemical properties of Alzheimer’s disease sarkosyl-insoluble tau. These new reagents will be useful for investigating the progression of tau pathology and further as tools to target the cellular transmission of tau pathology.
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影响因子：
14.5
作者：
Collin, Ludovic;Bohrmann, Bernd;Grueninger, Fiona
通讯作者：
Grueninger, Fiona
影响因子：
56.9
作者：
Hong, M;Zhukareva, V;Lee, VMY
通讯作者：
Lee, VMY
影响因子：
11.4
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
影响因子：
16.2
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
影响因子：
2.5
作者：
GOEDERT, M;JAKES, R;VANMECHELEN, E
通讯作者：
VANMECHELEN, E