AQP4 and early-onset autosomal dominant Alzheimer disease: It has also been shown that the appropriate expression pattern of AQP4 polarization to astrocytic endfeet is required for efficient glymphatic CSF-ISF exchange (Iliff et al., 2014; Kress et al., 2014; Hadjihambi et al., 2019), and that this polarization in the brain declines with age (Kress et al., 2014; Zeppenfeld et al., 2016), the greatest risk factor for developing Alzheimer’s disease (Guerreiro and Bras, 2015).