Considering that decreased production of NO—via reduced activity of constitutive NOS—is a known feature of endothelial dysfunction in physiological aging processes in humans [35], the increase in both eNOS and nNOS in APOE ε3 opens to many possible interpretations and might reflect the activation of a condition-specific compensative or detrimental mechanism activated by endothelial cells in response to protein misfolding in AD. This evidence concerns the gene NOS1 and Alzheimer disease.