AQP4 and Alzheimer disease: A pathological inter-relationship between neurodegenerative proteinopathies and the glymphatic system was first reported by Iliff et al., who connected a marked decrease (70% for [3H]mannitol) in interstitial solute clearance with increased levels of amyloid β, the main constituent of plaques in Alzheimer’s disease, in an AQP4-/- mouse model.