Use of proton pump inhibitors (PPIs) is associated with increased risk of dementia and cognitive impairment. Accumulating evidence indicate that the dysfunction of blood-brain barrier (BBB) in hippocampus was observed in the aged people with prior cognitive impairment, suggesting that BBB dysfunction precedes cognitive impairment. The primary responsibility of the BBB is regulating paracellular permeability to blood-borne substances including plasma proteins. Therefore, we hypothesized that PPIs impair brain endothelial barrier formed by tight junction to increase dementia risk. Here, we investigated whether vonoprazan, a potassium-competitive acid blocker, affects the brain endothelial expression of tight junction-associated proteins (claudin-5, occludin and ZO-1) to induce BBB dysfunction. Primary cultures of rat brain endothelial cells (RBECs) were used. RBECs were treated with vonoprazan (1-30 μM) for 24hr. Vonoprazan dose-dependently decreased mRNA and protein expression levels of claudin-5, occludin and ZO-1. mRNA levels of Icam-1 and Vcam-1 were not affected by vonoprazan, suggesting that vonoprazan decreased tight junction in RBECs independently of inflammatory process. These results suggest that vonoprazan could induce BBB dysfunction, leading to the increased risk of dementia.