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

•CPP prevent cognitive dysfunction in APP/PS2 mouse model of Alzheimer’s disease.•CPP reduce hippocampal Aβ deposition.•5-CQA, the main CPP component, degrades Aβ fibrils.•CPP have a therapeutic potential for treating cognitive deficits in AD. 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, 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 amyloid β (Aβ) plaques in the hippocampus. Furthermore, we determined that 5-caffeoylquinic acid, one of the primary coffee polyphenols, did not inhibit Aβ fibrillation; however, 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.