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 in preventing cognitive dysfunction induced by Alzheimer’s disease is limited. In this study, we investigated the effect of chlorogenic acids on 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. We found that chronic treatment with coffee polyphenols prevented cognitive dysfunction and significantly reduced hippocampal Aβ deposition. We then determined the effect of 5-caffeoylquinic acid, one of the primary components of coffee polyphenols, on Aβ formation. 5-Caffeoylquinic acid did not inhibit Aβ fibrillation, but degraded Aβ fibrils in a dose-dependent manner. In conclusion, these results demonstrate that coffee polyphenols prevented cognitive deficits and alleviated Aβ plaque deposition via disaggregation of Aβ in APP/PS2 mouse.

流行病学研究已证实，习惯性饮用咖啡可降低阿尔茨海默病（Alzheimer’s Disease）的发病风险。咖啡富含多种酚类化合物，即咖啡多酚（coffee polyphenols），例如绿原酸（chlorogenic acids）。然而，关于绿原酸在预防阿尔茨海默病诱发的认知功能障碍方面的相关证据仍较为有限。本研究以APP/PS2转基因小鼠模型（APP/PS2 transgenic mouse model）为研究对象，探究了绿原酸对阿尔茨海默病相关认知功能障碍的预防作用。研究人员对5周龄的APP/PS2小鼠每日喂食添加咖啡多酚的饲料，持续干预5个月。通过新物体识别实验（novel object recognition test）、莫里斯水迷宫实验（Morris water maze test）以及穿梭被动回避实验（step-through passive avoidance test），评估小鼠的记忆与认知功能。结果显示，长期咖啡多酚干预可有效改善认知功能障碍，并显著减少海马区Aβ沉积。随后，研究人员进一步分析了咖啡多酚的主要成分之一——5-咖啡酰奎宁酸（5-caffeoylquinic acid）对Aβ生成的影响。实验发现，5-咖啡酰奎宁酸并未抑制Aβ纤维化（Aβ fibrillation），而是以剂量依赖性方式降解Aβ纤维（Aβ fibrils）。综上，本研究结果表明，咖啡多酚可通过解聚Aβ，改善APP/PS2小鼠的认知缺陷并减轻Aβ斑块沉积。