Taking into account the progressive reduction in cerebral blood flow caused by carotid atherosclerosis and stenosis that was aggravated by a high cholesterol chow, our data suggested that the sustained hypoperfusion and hypercholesterolemia-induced changes in the cerebral microvasculature were synergized, resulting in cerebral microvascular endothelial activation manifested by upregulation of cell surface adhesion molecules, including ICAM-1, VCAM-1, and E-selectin. Here, ICAM1 is linked to familial hypercholesterolemia.