Apolipoprotein E-related lipoprotein clearance pathway

The APOE-related lipoprotein clearance pathway is a multi-component biological process responsible for the transport, redistribution, and removal of lipid-rich particles from the blood and the central nervous system (CNS) [1, 2]. This pathway is primarily mediated by Apolipoprotein E (APOE), which serves as a high-affinity ligand for several cell-surface receptors, including the low-density lipoprotein receptor (LDLR), LDL receptor-related protein 1 (LRP1), and very low-density lipoprotein receptor (VLDLR) [3, 7]. In the periphery, the pathway facilitates the hepatic clearance of chylomicron and VLDL remnants, thereby regulating plasma cholesterol and triglyceride levels [2, 5]. In the brain, APOE-containing lipoproteins are essential for lipid delivery to neurons and the clearance of metabolic byproducts, most notably amyloid-beta (Aβ) peptides [1, 7]. Dysregulation of this pathway, particularly in individuals carrying the APOE ε4 allele, is strongly associated with the pathogenesis of Alzheimer's disease and atherosclerosis due to inefficient Aβ clearance and impaired lipid homeostasis [10, 11]. Therapeutic interventions targeting this pathway include APOE structure correctors, ABCA1 agonists to enhance lipidation, and monoclonal antibodies or antisense oligonucleotides designed to modulate APOE levels or function [12, 13].

Other names

APOE-mediated lipoprotein clearanceAPOE-dependent remnant clearanceAPOE-receptor pathwayApolipoprotein E clearance pathway

Enhancement of APOE-mediated endocytosis and clearance of lipoproteins and amyloid-beta through receptor modulation, lipidation improvement, or structural correction of the APOE protein [11, 12].