NOS3 and Alzheimer disease: In AD, loss of eNOS contributes to cerebral blood vessels stiffening thereby diminishing clearance of Aβ and, in cultured human brain microvascular endothelium, increasing expression of β-amyloid protein precursor (AβPP) and β-site APP-cleaving enzyme 1 (BACE) thus favouring production of cytotoxic Aβ peptides25–27.