Upregulation of ET-1 production in AD seems likely to be secondary to the accumulation of Aβ, since exposure of SH-SY5Y human neuroblastoma cells and human brain microvascular endothelial cells to Aβ caused upregulation of ECE-2 and ECE-1, respectively, resulting in increased production and release into the supernatant of ET-1 (Palmer et al., 2009, 2012, 2013). This evidence concerns the gene EDN1 and Alzheimer disease.