When fed a high-fat diet (HFD) or HFD plus cholesterol, LDLr−/−.Leiden mice showed reduced CBF, endothelial dysfunction (lowered GLUT-1), elevated vascular inflammation (ICAM-1, VCAM-1, S-selectin), and BBB leakage, as evidenced by DCE-MRI and NaFl, together with reduced ZO-1 and claudin-5 expression. This evidence concerns the gene TJP1 and endothelial dysfunction.