Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, United States of America.
Center for Translational Research in Neurodegenerative Disease, College of Medicine University of Florida, Gainesville, FL, United States of America.
PLoS One. 2018 Apr 2;13(4):e0195211. doi: 10.1371/journal.pone.0195211. eCollection 2018.
Tauopathies including Alzheimer's disease and Progressive Supranuclear Palsy are a diverse group of progressive neurodegenerative disorders pathologically defined by inclusions containing aberrantly aggregated, post-translationally modified tau. The tau pathology burden correlates with neurodegeneration and dementia observed in these diseases. The microtubule binding domain of tau is essential for its physiological functions in promoting neuronal cytoskeletal stability, however it is also required for tau to assemble into an amyloid structure that comprises pathological inclusions. A series of novel monoclonal antibodies were generated which recognize the second and fourth microtubule-binding repeat domain of tau, thus enabling the identification specifically of 4-repeat tau versus 3-/4-repeat tau, respectively. These antibodies are highly specific for tau and recognize pathological tau inclusions in human tauopathies including Alzheimer's disease and Progressive Supranuclear Palsy and in transgenic mouse models of tauopathies. These new antibodies will be useful for identifying and characterizing different tauopathies and as tools to target tau pathology in these diseases.
包括阿尔茨海默病和进行性核上性麻痹在内的 tau 病是一组异质性的进行性神经退行性疾病，其病理学特征为包含异常聚集、翻译后修饰的 tau 的包涵体。tau 病理学负担与这些疾病中观察到的神经退行性变和痴呆相关。tau 的微管结合结构域对于其促进神经元细胞骨架稳定性的生理功能至关重要，但它也是 tau 组装成包含病理包涵体的淀粉样结构所必需的。生成了一系列新的单克隆抗体，这些抗体识别 tau 的第二个和第四个微管结合重复结构域，从而能够分别特异性识别 4 重复 tau 与 3/4 重复 tau。这些抗体对 tau 具有高度特异性，可识别包括阿尔茨海默病和进行性核上性麻痹在内的人类 tau 病以及 tau 病的转基因小鼠模型中的病理性 tau 包涵体。这些新的抗体将有助于鉴定和表征不同的 tau 病，并作为靶向这些疾病中 tau 病理学的工具。
