Apolipoprotein E and LDL receptor family (ApoE-LDLR family)

The Apolipoprotein E (ApoE) and LDL receptor (LDLR) family constitutes a critical biological axis responsible for the transport and metabolism of lipids and cholesterol throughout the body and the central nervous system. ApoE serves as a primary ligand for several members of the LDLR family, including the LDL receptor, LRP1, VLDLR, and ApoER2, facilitating the endocytosis of lipoprotein particles. In the periphery, this interaction is essential for maintaining plasma cholesterol levels, while in the brain, it plays a pivotal role in neuronal lipid delivery, synaptic maintenance, and the clearance of amyloid-beta peptides. Genetic variations in the APOE gene, particularly the ε4 allele, significantly increase the risk of Alzheimer's disease by impairing these clearance mechanisms and promoting neuroinflammation. Therapeutic strategies targeting this system include statins and PCSK9 inhibitors to lower cardiovascular risk, as well as emerging ApoE mimetics and gene therapies aimed at restoring or enhancing ApoE-mediated functions in neurodegenerative conditions.

Other names

ApoE-LDLR axisApolipoprotein E receptorsLow-density lipoprotein receptor familyApoE-binding receptors

Drugs targeting this system primarily work by upregulating the expression of LDL receptors (e.g., statins, PCSK9 inhibitors) to increase clearance of cholesterol-rich lipoproteins, or by mimicking/modulating the function of Apolipoprotein E (e.g., ApoE mimetics) to enhance lipid transport and amyloid-beta clearance in the brain.