In contrast to the apparently direct effects of Aβ42 on NO production, production of ET-1 is not increased by Aβ42 under RC-fed conditions in mice by direct infusion of WT mice with mouse Aβ42 or in AD mouse models overexpressing mutant human APP, but is increased by HF diet challenge, an action exacerbated by the presence of Aβ42. Here, EDN1 is linked to Alzheimer disease.