Tau interacts with α-Synuclein (α-Syn) and co-localizes with it in the Lewy bodies, influencing α-Syn pathology in Parkinson’s disease (PD). However, whether these biochemical events regulate α-Syn pathology spreading from the gut into the brain remains incompletely understood. Here, we show that α-Syn and Tau co-pathology is spread into the brain in gut-inducible SYN103+/− and/or TAU368+/− transgenic mouse models, eliciting behavioral defects. Gut pathology was initially observed, and α-Syn or Tau pathology was subsequently propagated into the DMV or NTS and then to other brain regions. Remarkably, more extensive spreading and widespread neuronal loss were found in double transgenic mice (Both) than in single transgenic mice. Truncal vagotomy and α-Syn deficiency significantly inhibited synucleinopathy or tauopathy spreading. The α-Syn PET tracer [18F]-F0502B detected α-Syn aggregates in the gut and brain. Thus, α-Syn and Tau co-pathology can propagate from the gut to the brain, triggering behavioral disorders.

中文翻译：

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肠道诱导的 α-突触核蛋白和 Tau 繁殖引发帕金森病和阿尔茨海默病的共病和行为障碍


Tau 与 α-突触核蛋白 （α-Syn） 相互作用并在路易体中与其共定位，影响帕金森病 （PD） 的 α-Syn 病理。然而，这些生化事件是否调节 α-Syn 病理学从肠道扩散到大脑仍不完全清楚。在这里，我们表明 α-Syn 和 Tau 共病理学在肠道诱导的 SYN103 + / - 和/或 TAU368 + / - 转基因小鼠模型中扩散到大脑中，引发行为缺陷。最初观察到肠道病理，随后 α-Syn 或 Tau 病理传播到 DMV 或 NTS，然后传播到其他脑区。值得注意的是，在双转基因小鼠 （Both） 中发现比单转基因小鼠更广泛的扩散和更广泛的神经元丢失。躯干迷走神经切断术和 α-Syn 缺陷显着抑制了突触核蛋白病或 tau 蛋白病的扩散。α-Syn PET 示踪剂 [18F]-F0502B 在肠道和大脑中检测到 α-Syn 聚集体。因此，α-Syn 和 Tau 联合病理可以从肠道传播到大脑，从而引发行为障碍。