Coffee polyphenols prevent cognitive dysfunction and suppress amyloid β plaques in APP/PS2 transgenic mousem

Epidemiological studies have found that habitual coffee consumption may reduce the risk of Alzheimer’s disease. Coffee contains numerous phenolic compounds (coffee polyphenols) such as chlorogenic acids. However, evidence demonstrating the contribution of chlorogenic acids to the prevention of cognitive dysfunction induced by Alzheimer’s disease is limited. The present study investigated the effect of chlorogenic acids on the prevention of cognitive dysfunction in APP/PS2 transgenic mouse model of Alzheimer’s disease. Five-week-old APP/PS2 mice were administered a diet supplemented with coffee polyphenols daily for 5 months. The memory and cognitive function of mice was determined using the novel object recognition test, the Morris water maze test, and the step-through passive avoidance test. Immunohistochemical analysis revealed that chronic treatment with coffee polyphenols prevented cognitive dysfunction and significantly reduced the amount of Aβ plaques in the hippocampus. We then determined that 5-caffeoylquinic acid, one of the primary components of coffee polyphenols, did not inhibit Aβ fibrillation but degraded Aβ fibrils. In conclusion, our results demonstrate that coffee polyphenols prevent cognitive deficits and reduce Aβ plaque deposition via disaggregation of Aβ in the APP/PS2 mouse.

流行病学研究表明，习惯性饮用咖啡或可降低阿尔茨海默病（Alzheimer’s disease）的发病风险。咖啡中含有多种酚类化合物（咖啡多酚），例如绿原酸。然而，目前能够证明绿原酸对预防阿尔茨海默病引发的认知功能障碍具有作用的相关证据仍较为有限。本研究以阿尔茨海默病APP/PS2转基因小鼠模型为研究对象，探究了绿原酸对认知功能障碍的预防效果。研究人员对5周龄的APP/PS2小鼠每日饲喂添加咖啡多酚的饲料，持续5个月。通过新物体识别实验、莫里斯水迷宫实验以及避暗被动回避实验，评估小鼠的记忆与认知功能。免疫组织化学分析结果显示，长期摄入咖啡多酚可预防认知功能障碍，并显著减少海马区内的Aβ斑块沉积量。后续研究发现，作为咖啡多酚主要成分之一的5-咖啡酰奎宁酸，并未抑制Aβ纤维的形成，反而可降解已形成的Aβ纤维。综上，本研究结果表明，在APP/PS2小鼠模型中，咖啡多酚可通过解聚Aβ，预防认知功能缺损并减少Aβ斑块沉积。