Department of Neurology, Washington University in St. Louis, St. Louis, MO 63105, USA.
School of Life Sciences, University of Sussex, Falmer BN1 9QG, UK.
Neuron. 2014 Jun 18;82(6):1271-88. doi: 10.1016/j.neuron.2014.04.047. Epub 2014 May 22.
Prion-like propagation of tau aggregation might underlie the stereotyped progression of neurodegenerative tauopathies. True prions stably maintain unique conformations ("strains") in vivo that link structure to patterns of pathology. We now find that tau meets this criterion. Stably expressed tau repeat domain indefinitely propagates distinct amyloid conformations in a clonal fashion in culture. Reintroduction of tau from these lines into naive cells reestablishes identical clones. We produced two strains in vitro that induce distinct pathologies in vivo as determined by successive inoculations into three generations of transgenic mice. Immunopurified tau from these mice recreates the original strains in culture. We used the cell system to isolate tau strains from 29 patients with 5 different tauopathies, finding that different diseases are associated with different sets of strains. Tau thus demonstrates essential characteristics of a prion. This might explain the phenotypic diversity of tauopathies and could enable more effective diagnosis and therapy.
tau 聚集的类朊病毒传播可能是神经退行性 tau 病刻板进展的基础。真正的朊病毒在体内稳定地保持独特的构象（“株”），将结构与病理模式联系起来。我们现在发现 tau 符合这一标准。稳定表达的 tau 重复结构域以克隆方式在培养物中无限传播独特的淀粉样纤维构象。从这些系中重新引入 tau 到未成熟细胞中，可重新建立相同的克隆。我们在体外产生了两种株，通过连续接种到三代转基因小鼠中，在体内诱导出不同的病理。从这些小鼠中免疫纯化的 tau 在培养物中重现了原始株。我们使用细胞系统从 29 名患有 5 种不同 tau 病的患者中分离 tau 株，发现不同的疾病与不同的株有关。tau 因此表现出朊病毒的基本特征。这可能解释了 tau 病的表型多样性，并能实现更有效的诊断和治疗。
