Pathology of Amyloid-β (Aβ) Peptide Peripheral Clearance in Alzheimer's Disease

Although Alzheimer's disease (AD) is traditionally viewed as a central nervous system disorder driven by the cerebral accumulation of toxic beta-amyloid (A beta) peptide, new interpretations of the amyloid cascade hypothesis have led to the recognition of the dynamic equilibrium in which A beta resides and the importance of peripheral A beta production and degradation in maintaining healthy A beta levels. Our review sheds light on the critical role of peripheral organs, particularly the liver, in the metabolism and clearance of circulating A beta. We explore the mechanisms of A beta transport across the blood-brain barrier (BBB) via transport proteins such as LRP1 and P-glycoprotein. We also examine how peripheral clearance mechanisms, including enzymatic degradation and phagocytic activity, impact A beta homeostasis. Our review also discusses potential therapeutic strategies targeting peripheral A beta clearance pathways. By enhancing these pathways, we propose a novel approach to reducing cerebral A beta burden, potentially slowing AD progression.