Lipid Transport and Metabolism at the Blood-Brain Interface: Implications in Health and Disease

Abstract

Many prospective studies have shown that a diet enriched in omega-3 polyunsaturated fatty acids (n-3 PUFAs) can improve cognitive function during normal aging and prevent the development of neurocognitive diseases. However, researchers have not elucidated how n-3 PUFAs are transferred from the blood to the brain or how they relate to cognitive scores. Transport into and out of the central nervous system depends on two main sets of barriers: the blood-brain barrier (BBB) between peripheral blood and brain tissue and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) between the blood and the CSF. In this review, the current knowledge of how lipids cross these barriers to reach the CNS is presented and discussed. Implications of these processes in health and disease, particularly during aging and neurodegenerative diseases, are also addressed. An assessment provided here is that the current knowledge of how lipids cross these barriers in humans is limited, which hence potentially restrains our capacity to intervene in and prevent neurodegenerative diseases.

Keywords: blood-brain-barrier; blood-cerebrospinal fluid barrier; cholesterol; lipid transport; n-3 PUFA.

FIGURE 1

Lipid transport at the blood-brain barrier. The top right corner shows a schematic representation of the blood-brain barrier (BBB) with the blood capillary, a pericyte, an astrocyte end-foot and a neuron. The rest of the figure (a magnified view of the black rectangle) illustrates the three ways lipids can cross the BBB: passive diffusion, transport using transmembrane proteins and transcytosis. Fatty acids (FAs) are locally produced in the endothelium after the hydrolysis of lipoproteins by membrane-associated lipase enzymes. FAs can either passively diffuse across the endothelial membrane or be transferred inside the endothelium by the activity of a transmembrane protein. Once in the endothelium of the BBB, FAs shuttle through the cytosol by binding to FA-binding proteins before being transported into the brain. Lipoproteins can also be directly transported into the brain via receptor-mediated transcytosis involving either caveolin- or clathrin-coated vesicles.

FIGURE 2

Cholesterol transport at the blood-CSF barrier. Schematic representation of cholesterol transport from the circulating blood to the CSF across the blood-CSF barrier. CPEC, choroid plexus epithelial cell; CSF, cerebrospinal fluid; Chol, cholesterol; VLDL, very low-density lipoprotein; Apo, apolipoprotein.