The mechanisms underlying such association might be complex (Figure 3): during brain aging, hypertension and the loss of AQP-4 water channels could impair the drainage of local interstitial fluid, and disrupt alpha-synuclein clearance (Peng et al., 2016; Lenck et al., 2018), for which the perivascular spaces function as an important pathway (Zou et al., 2019). Here, AQP4 is linked to hypertensive disorder.