Recent studies suggest that misfolded tau molecules can be released, and taken up by adjacent neurons, propagating proteopathic seeds across neural systems. Yet critical to understanding whether tau propagation is relevant in pathophysiology of disease would be to learn if it alters neuronal properties. We utilized high resolution multi-color in situ hybridization technology, RNAScope, in a well-established tau transgenic animal, and found that a subset of neurons in the cortex do not appear to express the transgene, but do develop phospho-tau positive inclusions, consistent with having received tau seeds. Recipient neurons show decreases in their expression of synaptophysin, CAMKIIα, and mouse tau in both young and old animals. These results contrast with neurons that develop tau aggregates and also overexpress the transgene, which have few changes in expression of metabolic and synaptic markers. Taken together, these results strongly suggest that tau propagation impacts neuronal functional integrity.

中文翻译：

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作为蛋白病 tau 种子受体的神经元的突触和代谢基因表达改变

最近的研究表明，错误折叠的 tau 分子可以被释放，并被相邻的神经元吸收，从而在整个神经系统中传播蛋白病种子。然而，了解 tau 传播是否与疾病的病理生理学相关的关键是了解它是否改变了神经元特性。我们在成熟的 tau 转基因动物中使用高分辨率多色原位杂交技术 RNAScope，发现皮质中的一部分神经元似乎不表达转基因，但确实产生了磷酸化 tau 阳性包涵体，与收到 tau 种子一致。受体神经元在年轻和年老动物中的突触素、CAMKIIα 和小鼠 tau 蛋白的表达均有所下降。这些结果与形成 tau 聚集体并过度表达转基因的神经元形成对比，代谢和突触标记物的表达几乎没有变化。总之，这些结果强烈表明 tau 传播影响神经元功能完整性。