Abstract:
Although Alzheimer’s disease (AD) is traditionally viewed as a central nervous system
disorder driven by the cerebral accumulation of toxic beta-amyloid (Aβ) peptide, new interpretations
of the amyloid cascade hypothesis have led to the recognition of the dynamic equilibrium in which
Aβ resides and the importance of peripheral Aβ production and degradation in maintaining healthy
Aβ levels. Our review sheds light on the critical role of peripheral organs, particularly the liver,
in the metabolism and clearance of circulating Aβ. We explore the mechanisms of Aβ 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 Aβ homeostasis. Our review also discusses potential therapeutic strategies targeting
peripheral Aβ clearance pathways. By enhancing these pathways, we propose a novel approach to
reducing cerebral Aβ burden, potentially slowing AD progression.
