Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation
Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation
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DOI：
10.1016/j.celrep.2015.04.043
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发表时间：
2015-05-26
期刊：
影响因子：
8.8
通讯作者：
Moechars, Diederik
中科院分区：
文献类型：
--
作者：
Calafate, Sara;Buist, Arjan;Moechars, Diederik
不溶性tau蛋白聚集体的积累和tau病理通过大脑的刻板印象传播是包括阿尔茨海默氏病（AD）在内的陶氏病的常见标志。 tau病理的传播似乎沿着连接的神经元发生，但是尚未证明神经元之间的突触接触是否促进传播。使用定量的体外模型，我们证明，与非突触机制并行突触，而不仅仅是细胞之间的近距离距离，增强了受体海马神经元和tau供体细胞之间TAU病理的传播。同样，在使用微流体设备的人工神经元网络中，突触和突触活动正在促进与非突触机制并行的神经元TAU病理传播。我们的工作表明，神经元之间的突触接触的物理存在促进了tau病理的传播。这些发现可能对突触修复疗法有影响，这可能会通过促进tau病理的传播而产生不利影响。
Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer's disease (AD). Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.