Preclinical studies of PDE5 inhibitors in cellular and animal models including AD, senescence, ischemic stroke [15], chronic cerebral hypoperfusion [16], and Huntington’s disease (HD) [17], etc. showed promising polypharmacological effects on neuroprotection, anti-inflammation, abnormal protein (Aβ and hyper-phosphorylated tau) depositions, regulation of ion channels, cerebrovascular maintenance, and cognitive functions [4, 18-21]. The gene discussed is MAPT; the disease is Huntington disease.