作为阿尔茨海默病（AD）的主要病理特征，Aβ异常沉积与脑类淋巴通道功能障碍有关。“肠-脑轴”可促进Aβ沉积，但机制不清。前期研究发现：运动训练促进类淋巴通道功能，减少Aβ沉积；肠道T淋巴细胞可在脑膜聚集并介导脑内炎症反应。预实验结果显示：肠道凋亡相关微粒蛋白（ASC）损伤脑膜淋巴内皮细胞，损害老年小鼠认知功能；运动训练增加Sirtuin-1蛋白的表达，改善“肠-脑轴”介导的认知功能障碍。因此，我们假设：运动训练可通过Sirtuin-1蛋白降低“肠-脑轴”中ASC的活性，提高Aβ经脑类淋巴通道清除效率，进而改善AD小鼠的认知功能。本研究拟采用APP/PS1转基因小鼠制备“肠-脑轴”运动训练模型，探讨运动训练是否通过抑制ASC活性，改善“肠-脑轴”介导的小鼠认知功能障碍，并明确Sirtuin-1蛋白的作用机制。研究结果可为深入阐明运动训练改善AD认知功能的机制及优化AD的康复策略提供依据。

As the major pathological character of Alzheimer’s disease, Aβ deposition is related to glymphatic dysfunction. “Gut-brain axis” aggravates the Aβ accumulation, but the mechanism has kept unknown. We previously found that: exercise accelerates the glymphatic clearance and decreases the Aβ deposits; T cells derived from gut were found in the meninges, which induced brain inflammation. The preliminary experiment showed that: Intestinal apoptosis associated speck-like protein (ASC) damaged the meningeal lymphoid endothelial cells and impaired the cognition in aged mice. Exercise increased the expression of Sirtuin-1 and improved cognition regulated by “gut-brain axis”. Therefore, we propose that: By activating sirtuin-1 signaling, Exercise inhibits the ASC activation, accelerates the glymphatic clearance and improves the cognition in AD mice. In this project, we will use APP/PS1 transgenic mice to induced the “gut-brain axis” training model, to elaborate the effect of physical training on the activation of ASC in “gut-brain axis” as well as on the cognition impaired by “gut-brain axis”, and define the mechanism of sirtuin-1. Our results will provide evidence for exercise is an effective treatment for cognition impairment in AD patients.