Glymphatic dysfunction in Alzheimer’s disease: A critical appraisal

Thirteen years after the initial publication defining the glymphatic system, we critically reappraise the role of its dysfunction in Alzheimer’s disease (AD). Our understanding of glymphatic function and its involvement in the pathogenesis of AD derives primarily from correlative clinical data and rodent studies. A causal role for glymphatic dysfunction in AD has not yet been established in humans. We review current approaches to assess glymphatic function clinically, which capture different features of perivascular fluid dynamics or their results. The absence of clinically suitable imaging approaches to measuring glymphatic exchange in the human brain is an obstacle to evaluating whether glymphatic function is impaired in AD populations and to developing and evaluating therapeutics to modulate glymphatic function in the treatment and prevention of AD.