Tau aggregation and hyperphosphorylation is a key neuropathological hallmark of Alzheimer's disease (AD), and the temporospatial spread of Tau observed during clinical manifestation suggests that Tau pathology may spread along the axonal network and propagate between synaptically connected neurons. Here, we have developed a cellular model that allows the study of human AD-derived Tau propagation from neuron to neuron using microfluidic devices. We show by using high-content imaging techniques and an in-house developed interactive computer program that human AD-derived Tau seeds rodent Tau that propagates trans-neuronally in a quantifiable manner in a microfluidic culture model. Moreover, we were able to convert this model to a medium-throughput format allowing the user to handle 16 two-chamber devices simultaneously in the footprint of a standard 96-well plate. Furthermore, we show that a small molecule inhibitor of aggregation can block the trans-neuronal transfer of Tau aggregates, suggesting that the system can be used to evaluate mechanisms of Tau transfer and find therapeutic interventions.

中文翻译：

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阿尔茨海默氏病脑中组装的人Tau在微流控神经元培养物中的定量繁殖。

Tau聚集和磷酸化过高是阿尔茨海默氏病（AD）的关键神经病理学标志，在临床表现期间观察到的Tau颞pat骨扩散表明Tau病理学可能沿轴突网络传播并在突触连接的神经元之间传播。在这里，我们开发了一种细胞模型，该模型可以使用微流控设备研究人类AD衍生的Tau从神经元传播到神经元的过程。我们显示通过使用高内涵的成像技术和内部开发的交互式计算机程序，人类AD衍生的Tau种子啮齿动物Tau可以以可量化的方式在微流控培养模型中跨神经元传播。此外，我们能够将该模型转换为中通量格式，从而允许用户在标准96孔板的占地面积内同时处理16个两室设备。此外，我们表明，聚集的小分子抑制剂可以阻止Tau聚集体的跨神经元转移，这表明该系统可用于评估Tau转移的机制并找到治疗性干预措施。