Aim: Amyloid β (Aβ) deposition in the brain is a major pathological feature of Alzheimer's disease (AD). In our previous study, we showed that coffee polyphenols (CPP) prevent cognitive decline and Aβ accumulation in the brain of an APP/PS2 transgenic mouse AD model. However, the underlying mechanisms remain to be elucidated. In the present study, we investigated the effects of the long-term administration of 5-caffeoylquinic acid (5-CQA), the most abundant component of CPP, on cognitive dysfunction in APP/PS2 mice to clarify the role of CPP in Aβ elimination.  
Results: The mice fed a 5-CQA-supplemented diet showed significant improvements in their cognitive function assessed by Y-maze and novel object recognition tests compared to the untreated controls. Histochemical analysis disclosed that 5-CQA substantially reduced Aβ plaque formation and neuronal loss in the hippocampi. Furthermore, 5-CQA upregulated the gene expression of LRP-1, an Aβ efflux receptor, and normalized the perivascular localization of AQP4, which facilitates Aβ clearance along the paravascular pathway.
Conclusions: These results indicate that 5-CQA decreases Aβ deposition in the brain by modulating the Aβ clearance pathways and ameliorating cognitive decline and neuronal loss in APP/PS2 mice. Thus, 5-CQA may be effective in preventing cognitive dysfunction in AD.