In Alzheimer’s disease Loss of AQP4 polarity occurs when AQP4 expression is mislocalized within astrocytes, becoming broadly distributed rather than concentrated at the perivascular end feet, impairing its efficiency in fluid transport and waste clearance, which exacerbates the accumulation of amyloid-β, contributing to the progression of Alzheimer’s disease pathology. The gene discussed is AQP4; the disease is early-onset autosomal dominant Alzheimer disease.