The first one isrelated to the “neurovascular theory”, based onthe fact that microvascular injuries may reduce amyloid clearancethrough altered delivery of nutrients to neurons.39 Endothelial dysfunction has been highlighted in AD patients,even if the cause–effect relationship is not fully understood.40 Here relies the potential of PDE5 inhibitors,since they act by relaxing the arterial wall and improving endothelialfunctioning via the NO-cGMP pathway. The gene discussed is PDE5A; the disease is Alzheimer disease.