Reduced oxygenation of theprecuneus is evident at an early stage of AD (i.e. Braak tangle stage III-IV disease),26 and correlates strongly with the level of endothelin-1 (EDN1), a potentvasoconstrictor, which is increased in AD,26,27,29 probably as a consequence ofAβ42-mediated upregulation of endothelin-converting enzyme-2 (ECE-2),30 but Aβ40-mediated upregulation of ECE-1 may also contribute.29 The gene discussed is EDN1; the disease is Alzheimer disease.