Factors affecting aquaporin-4 and its regulatory mechanisms in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disorder, with its core pathological features being the excessive deposition of amyloid-beta (Aβ) protein and the abnormal phosphorylation of tau protein. This review introduces the crucial role of aquaporin-4 (AQP4) in AD, particularly in the glymphatic system, where it facilitates the clearance of Aβ and other metabolic waste. It describes the structure and function of AQP4, its involvement in AD, and the factors affecting it, including Aβ, tau protein, glutamate transporters, adenosine, exercise, sleep, and diet. The article reviews the relationship between the loss of AQP4 polarity and the reduced efficiency of Aβ clearance and summarizes potential therapeutic strategies to restore AQP4 polarity to enhance waste clearance. The authors point out that AQP4 holds great potential as a therapeutic target for AD, propose the possibility of restoring AQP4 function through drug interventions and lifestyle adjustments, and suggest that further research into AQP4 regulatory mechanisms will provide new directions and insights for the prevention and treatment of AD.