阿尔茨海默病（AD）是一种以进行性认知功能下降为临床特征的神经系统退行性疾病，主要由脑内错误折叠蛋白的异常聚集引起，但针对错误折叠蛋白的特异性抗体和抑制其产生的药物试验均以失败告终。因此，如何将错误折叠蛋白转运至外周降解成为治疗AD最有潜力的靶点之一。外泌体是一种具有独特脂质双层结构的微小囊泡，易透过血脑屏障，是介导中枢错误折叠蛋白转运的绝佳载体。项目组前期研究结果证实有氧运动后AD小鼠脑内外泌体含量明显增加，且认知功能及神经病理损伤明显改善。在此基础上，项目组拟进一步明确有氧运动对AD小鼠外周和脑内外泌体含量的影响，并侧重于检测有氧运动AD小鼠血清外泌体中错误折叠蛋白的表达量和代谢。项目组还将进一步采用外泌体释放特异性抑制剂验证阻断外泌体释放是否可有效逆转有氧运动对AD小鼠的认知改善作用。本项目的完成将为AD的防治提供一种有效的非药物治疗手段，为今后临床防治AD提供新的策略。

Alzheimer's disease (AD), characterized by progressive decline of cognitive function, is a degenerative disease mainly caused by the abnormal aggregation of misfolded proteins in the brain; however, the clinical drug trials all ended in failure, neither specific antibodies against misfolded proteins nor drugs suppressing its production. Therefore, it becomes one of the most possible therapeutic targets of AD to efficiently transfer the misfolded proteins from brain to the peripheral circulation. Exosome, as the small vesicle with unique lipid bilayer structure, can easily cross the blood brain barrier, and therefore, is an excellent carrier for the transfer of misfolded proteins. Our preliminary results showed that the aerobic exercise significantly increased the exosomes in the AD mice brain, improved the cognitive function and reduced the amyloid beta deposition compared with the control mice. Based on the previous study, the quantity and content of exosome in the brain and peripheral blood serum will be further investigated after aerobic exercise. The specific exosome inhibitor will be used to further validate whether the inhibition of the exosome release could effectively reverse the improvement of cognitive function in AD mice with aerobic exercise. This project will provide a feasible non-drug treatment and offer a new strategy for clinical prevention and cure of AD.