High-density lipoproteins at the interface between central nervous system and plasma lipoprotein metabolism

Abstract

The brain is the most lipid-rich organ in the body and contains 25% of the body’s total cholesterol content. ApoE is the major apolipoprotein expressed in the brain and genetic variations in apoE underlie much of the genetically determined risk of late-onset Alzheimer’s disease. Regulation of lipid homeostasis in the CNS is therefore of great interest for healthy brain aging. The brain’s lipid transport system is built around lipoprotein particles that are similar in size and presumed function to circulating HDL. It is increasingly appreciated that many comorbidities that increase Alzheimer’s disease risk include aspects of aberrant HDL-metabolism, yet how circulating HDL may impact brain health is not fully understood. As comprehending the similarities and differences between CNS and peripheral lipid metabolism may reveal important relationships between cardiovascular and neurological diseases, here we review the fundamental properties of HDL metabolism in both peripheral and CNS compartments.

Keywords:

• apoA-I
• apoE
• brain
• cerebrospinal fluid
• clusterin/apoJ
• complement
• HDL
• inflammation
• proteome