Among varieties of vasoactive drugs, cilostazol, a selective inhibitor of type 3 phosphodiesterase (PDE), is likely to be a promising agent for AD and CAA (Figure 3). PDE3 can hydrolyze both cAMP and cGMP, while increasing cAMP level is a major pharmacological effect of cilostazol (Ikeda, 1999). PDE3 is widely expressed in central nervous system and up-regulated in Aβ-positive vessels, especially in vascular smooth muscle cells (vSMC) (Maki et al., 2014), suggesting the possibility that PDE3 inhibition could be therapeutic for CAA. Cilostazol possesses multiple effects, such as increasing pulse rate (Shinohara et al., 2010) and arterial elasticity (Han et al., 2013), prolonging pulse duration time (Aruna and Naidu, 2007), and dilating cerebral vessels (Tanaka et al., 1989; Birk et al., 2004a,b); such vasoactive actions may promote efficiency of perivascular drainage. In support of this, clearance of fluorescent soluble Aβ tracers is significantly enhanced in cilostazol-treated CAA model mice, thereby resulting in maintenance of vascular integrity, amelioration of Aβ deposits (Figure 4), and prevention of cognitive decline (Maki et al., 2014). Memory-preserving activity of cilostazol has been demonstrated in aged
