The primary clinical effects of PDE5I are a result of raised cyclic guanosine monophosphate (cGMP), a secondary messenger that is degraded by the phosphodiesterase enzyme (PDE).9 The relationship between the levels of cGMP and memory has been explored previously, with studies showing low levels of cGMP in tandem with raised levels of PDE in the brains of people with AD.10,11 These findings have led to several PDE5I studies in animal models, which have demonstrated possible neuroprotective benefits.12 However, evidence of neuroprotective effects in humans is not conclusive. The gene discussed is ALDH7A1; the disease is Alzheimer disease.