Therapeutic plasma exchange in Alzheimer's disease: From clinical trial to real-world evidence.

This article examines the expanding role of therapeutic plasma exchange (TPE) in Alzheimer's disease (AD), alongside recent developments in diagnostic approaches, disease mechanisms, and emerging disease-modifying treatments. Although AD has historically been considered a disorder defined by amyloid and tau pathology, contemporary models increasingly emphasize a multifactorial systems-biology framework that includes immune dysregulation, oxidative stress, vascular injury, impaired protein clearance, and synaptic dysfunction. Within this evolving model, TPE has emerged as a biologically rational, broadly acting therapeutic strategy that contrasts mechanistically with selective anti-amyloid monoclonal antibodies. This article reviews the global burden of AD and the need for safer disease-modifying therapies; current understanding of AD pathophysiology and biomarker-based diagnosis; available symptomatic and disease-modifying treatments; the AMBAR trial and the earlier pilot work that supported it; real-world cohort evidence; the author's clinical experience with TPE in AD; the mechanism of action of TPE in comparison with anti-amyloid monoclonal antibodies; the evolution of TPE from acute hospital-based therapy to chronic outpatient disease management; and future directions for TPE in neurodegenerative disease.