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.

The accumulation of amyloid β (Aβ) in the brain is a major pathological feature of Alzheimer’s disease (AD). In our previous study, we demonstrated that coffee polyphenols (CPP) prevent cognitive dysfunction and Aβ deposition in the brain of an APP/PS2 transgenic mouse AD model. The underlying mechanisms, however, remain to be elucidated. Here, we investigated the effects of the chronic administration of 5-caffeoylquinic acid (5-CQA), the most abundant component of CPP, on cognitive dysfunction in APP/PS2 mice to identify the role of CPP in Aβ elimination. Relative to the untreated controls, the mice fed a 5-CQA-supplemented diet showed significant improvements in their cognitive function assessed by Y-maze and novel object recognition tests. Histochemical analysis revealed that 5-CQA substantially reduced Aβ plaque formation and neuronal loss in the hippocampi. Moreover, 5-CQA upregulated the gene encoding low-density lipoprotein receptor-related protein 1, an Aβ efflux receptor, and normalized the perivascular localization of aquaporin 4, which facilitates Aβ clearance along the paravascular pathway. These results suggest that 5-CQA reduces 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.

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.

Habitual consumption of chlorogenic acid compounds (CGAs) from coffee increases fat catabolism and reduces body fat; however, the contribution of roasted coffee remains unclear. Hydroxyhydroquinone (HHQ) impairs the vasodilatory and antihypertensive effects of CGAs by reducing nitric oxide (NO) bioavailability. Since HHQ also reduces fat catabolism, we hypothesized that HHQ does so by decreasing NO availability. Therefore, we investigated the effect of HHQ on energy metabolism in KKAy mice. In HHQ-treated mice, fat oxidation was significantly low and dose-dependent, serum and urinary hydrogen peroxide were high, and plasma NO metabolites and S-nitrosylated liver proteins were low. In HHQ-treated mouse hepatocytes, the palmitate-induced increase in cellular oxygen consumption was negatively affected, and HHQ or L-NAME reduced cellular fatty acid utilization. In conclusion, HHQ can impair fat utilization by reducing NO availability in mice. Protein S-nitrosylation reduction in liver cells after HHQ consumption may be associated with impaired fatty acid oxidation.