The effect of Claudin-5-targeting ligands on blood-brain barrier (BBB) integrity can be studied further utilizing cell-based permeability models, such as the hCMEC/D3 human brain endothelial monolayer system.For in vivo validation, well-established vascular dementia models, such as bilateral common carotid artery occlusion (BCCAO) in rats and chronic cerebral hypoperfusion in mice, can be used. The gene discussed is CLDN5; the disease is vascular dementia.