Faculté de Médecine, Département de Psychiatrie et Neurosciences, Université Laval, Quebec, QC, Canada.
Centre de Recherche du CHU de Québec - Université Laval, Axe Neurosciences, Quebec, QC, Canada.
Methods Mol Biol. 2024;2754:323-341. doi: 10.1007/978-1-0716-3629-9_17.
The intracellular accumulation of microtubule-associated protein tau is a characteristic feature of tauopathies, a group of neurodegenerative diseases including Alzheimer's disease. Formation of insoluble tau aggregates is initiated by the abnormal hyperphosphorylation and oligomerization of tau. Over the past decades, multiple transgenic rodent models mimicking tauopathies have been develop, showcasing this neuropathological hallmark. The biochemical analysis of insoluble tau in these models has served as a valuable tool to understand the progression of tau-related pathology. In this chapter, we provide a comprehensive review of the two primary methods for isolating insoluble tau, namely, sarkosyl and formic acid extraction (and their variants), which are employed for biochemical analysis in transgenic mouse models of tauopathy. We also analyze the strengths and limitations of these methods.
细胞内微管相关蛋白 tau 的积累是 tau 病的一个特征,tau 病是一组包括阿尔茨海默病在内的神经退行性疾病。tau 的异常过度磷酸化和寡聚化引发了不溶性 tau 聚集物的形成。在过去的几十年中,已经开发出多种模拟 tau 病的转基因啮齿动物模型,展示了这种神经病理学特征。这些模型中不溶性 tau 的生化分析已成为了解 tau 相关病理学进展的有价值工具。在本章中,我们全面回顾了用于分离不溶性 tau 的两种主要方法,即 sarcosyl 和甲酸提取(及其变体),它们用于 tau 病转基因小鼠模型的生化分析。我们还分析了这些方法的优缺点。