Translational Neuroimaging Laboratory (TNL), McGill Center for Studies in Aging, Douglas Mental Health University Institute, McGill University, 6875 La Salle Blv - FBC room 3149, Montreal, QC, H4H 1R3, Canada.
Montreal Neurological Institute (MNI), Montreal, Canada.
Transl Neurodegener. 2014 Mar 15;3(1):6. doi: 10.1186/2047-9158-3-6.
Hyperphosphorylation of the tau protein leading to the formation of neurofibrillary tangles (NFTs) is a common feature in a wide range of neurodegenerative diseases known as tauopathies, which include Alzheimer's disease (AD) and the frontotemporal dementias (FTDs). Although heavily investigated, the mechanisms underlying the pathogenesis and progression of tauopathies have yet to be fully understood. In this context, several rodent models have been developed that successfully recapitulate the behavioral and neurochemical features of tau pathology, aiming to achieve a better understanding of the link between tau and neurodegeneration. To date, behavioral and biochemical parameters assessed using these models have been conducted using a combination of memory tasks and invasive methods such as cerebrospinal fluid (CSF) sampling or post-mortem analysis. Recently, several novel positron emission tomography (PET) radiopharmaceuticals targeting tau tangles have been developed, allowing for non-invasive in vivo quantification of tau pathology. Combined with tau transgenic models and microPET, these tracers hold the promise of advancing the development of theoretical models and advancing our understanding of the natural history of AD and non-AD tauopathies. In this review, we briefly describe some of the most important insights for understanding the biological basis of tau pathology, and shed light on the opportunity for improved modeling of tau pathology using a combination of tau-radiopharmaceuticals and animal models.
过度磷酸化的 tau 蛋白导致神经原纤维缠结（NFTs）的形成是广泛的神经退行性疾病的一个共同特征，这些疾病被称为 tau 病，包括阿尔茨海默病（AD）和额颞叶痴呆（FTDs）。尽管已经进行了大量研究，但 tau 病的发病机制和进展的机制尚未完全理解。在这种情况下，已经开发了几种啮齿动物模型，这些模型成功地再现了 tau 病理学的行为和神经化学特征，旨在更好地理解 tau 与神经退行性变之间的联系。迄今为止，使用这些模型评估的行为和生化参数一直是通过结合记忆任务和侵入性方法（如脑脊液（CSF）采样或死后分析）来进行的。最近，已经开发了几种针对 tau 缠结的新型正电子发射断层扫描（PET）放射性药物，允许对 tau 病理学进行非侵入性的体内定量。与 tau 转基因模型和 microPET 结合使用，这些示踪剂有望推进理论模型的发展，并深入了解 AD 和非 AD tau 病的自然史。在这篇综述中，我们简要描述了一些理解 tau 病理学生物学基础的最重要的见解，并阐明了使用 tau 放射性药物和动物模型组合来改进 tau 病理学建模的机会。
