コーヒーポリフェノールはアルツハイマー型認知症モデルマウス（APP/PS2）のアミロイドβ蓄積および認知機能障害を抑制する

抄録

Epidemiological studies have revealed that habitual coffee consumption may reduce the risk of Alzheimer’s disease. Coffee includes many phenolic compounds (coffee polyphenols) such as chlorogenic acids. However, the contribution of chlorogenic acids to the prevention of cognitive dysfunction induced by Alzheimer’s disease remains obscure. In this study, we investigated the effect of chlorogenic acids on cognitive function 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 examined using the novel object recognition test, Morris water maze test, and the step-through passive avoidance test. Chronic treatment with coffee polyphenols prevented cognitive dysfunction and significantly reduced the amount of amyloid β (Aβ) plaques in the hippocampus. Moreover, 5-caffeoylquinic acid (5-CQA), one of the primary coffee polyphenols, did not inhibit Aβ fibrillation; however, degraded Aβ fibrils. Computational docking simulation predicted that 5-CQA interacted with specific amino acid residues in Aβ protofilament.  In conclusion, our results demonstrate that coffee polyphenols prevent cognitive dysfunction and reduce Aβ plaque deposition via disaggregation of Aβ in the APP/PS2 mouse.