Moreover, as BNP is a potent vasodilator [52], one could speculate that physiological attempts at increasing BNP levels in the AD subjects who are APOE4 carriers (Fig 3), may improve cerebral perfusion in a diseased brain, in case the peripheral BNP crosses the blood-brain-barrier thereby entering the brain to exert its vasodilatory effects. The gene discussed is NPPB; the disease is Alzheimer disease.