Tau Prion Strains Dictate Patterns of Cell Pathology, Progression Rate, and Regional Vulnerability In Vivo.
Tau Prion Strains Dictate Patterns of Cell Pathology, Progression Rate, and Regional Vulnerability In Vivo.
复制标题
DOI：
10.1016/j.neuron.2016.09.055
复制
发表时间：
2016-11-23
期刊：
影响因子：
16.2
通讯作者：
Diamond MI
中科院分区：
文献类型：
--
作者：
Kaufman SK;Sanders DW;Thomas TL;Ruchinskas AJ;Vaquer-Alicea J;Sharma AM;Miller TM;Diamond MI
tau病是一种神经退行性疾病，影响不同的大脑区域，以不同的速度发展，并表现出特定的tau积累模式。这种多样性的来源尚不清楚。我们之前描述了两种在体外和体内稳定保持独特构象的tau菌株，但没有确定每种菌株与区分tau病的参数（如区域易感性或传播率）的关系。我们现在已经根据详细的生化和生物学标准在细胞中分离和表征了18个tau菌株。用这些菌株接种转基因tau P301S （PS19）小鼠，在不同的细胞类型和脑区引起菌株特异性的细胞内病理，并诱导不同的网络传播速率。在这个系统中，菌株本身就足以解释不同的神经病理表现，类似于那些定义人类牛头病的神经病理表现。因此，对这些菌株的进一步研究可以建立控制这些生物效应的结构逻辑。
Tauopathies are neurodegenerative disorders that affect distinct brain regions, progress at different rates, and exhibit specific patterns of tau accumulation. The source of this diversity is unknown. We previously characterized two tau strains that stably maintain unique conformations in vitro and in vivo, but did not determine the relationship of each strain to parameters that discriminate between tauopathies such as regional vulnerability or rate of spread. We have now isolated and characterized 18 tau strains in cells based on detailed biochemical and biological criteria. Inoculation of transgenic tau P301S (PS19) mice with these strains causes strain-specific intracellular pathology in distinct cell types and brain regions, and induces different rates of network propagation. In this system, strains alone are sufficient to account for diverse neuropathological presentations, similar to those that define human tauopathies. Further study of these strains can thus establish a structural logic that governs these biological effects.