Over-expressed RAGE on blood vessel endothelial cells can activate the membrane-transporting system of AGE-RAGE and Aβ, resulting in accumulation of AGEs and Aβ in parenchyma and release of ET-1, which is reported in diabetic microangiopathy and Alzheimer's disease (AD) [13], [14], [15]. This evidence concerns the gene EDN1 and Alzheimer disease.