Mechanisms linking apolipoprotein E isoforms with cardiovascular and neurological diseases

Abstract

The purpose of this review is to provide insights into recent advances in mechanisms linking apolipoprotein (apo) E isoforms to cardiovascular and neurological diseases. Human apoE has three common isoforms (apoE2, apoE3, and apoE4) with different structural and biophysical properties and different effects on lipid and neuronal homeostasis. ApoE is a protein constituent of different plasma lipoproteins and serves as a high-affinity ligand for several receptors. By interacting with its receptors, apoE mediates the clearance of different lipoproteins from the circulation. Absence or structural mutations of apoE cause significant disorders in lipid metabolism and cardiovascular disease. ApoE also has significant roles in neurobiology. ApoE4 is the major known genetic risk factor for Alzheimer's disease. It increases the occurrence and lowers the age of onset of Alzheimer's disease. ApoE4 carriers account for 65-80% of all Alzheimer's disease cases, highlighting the importance of apoE4 in Alzheimer's disease pathogenesis. ApoE4 has both amyloid beta-dependent and amyloid beta-independent roles in Alzheimer's disease pathogenesis. Emerging data suggest that apoE isoforms, with their multiple cellular origins and multiple structural and biophysical properties, contribute to cardiovascular and neurological diseases by interacting with different factors through various pathways.