CEREBROSPINAL-FLUID LIPOPROTEINS, LIPOPROTEIN RECEPTORS, AND NEURITE OUTGROWTH

Apolipoprotein (apo-) E, a ligand for members of the low density lipop rotein (LDL) receptor gene family, is present in cerebrospinal fluid ( CSF) at approximately 5% of its plasma concentration. Since the CSF al so contains apo-AI but not apo-B, apo-E is the only apolipoprotein in CSF capable of interacting with the LDL receptor or other members of t his receptor family that are expressed by various cells in the brain: the LDL receptor-related protein (LRP), the very low density lipoprote in receptor, and apo-E receptor 2. The apo-E and ape-Al occur predomin antly on separate lipoprotein particles with densities similar to thos e of a subclass of plasma high density lipoproteins, HDL,. The CSF apo -E is produced by astrocytes within the brain. The CSF apo-E, apo-E se creted by astrocytes, and apo-E present in brain tissue are more highl y sialylated than plasma apo-E but still bind lipoprotein receptors wi th high affinity One apo-E isoform, apo-E4, is associated with increas ed risk of developing Alzheimer's disease. In in vitro studies, apo-E4 together with CSF lipoproteins inhibits neurite outgrowth from neurob lastoma cells (Neuro-2a), whereas apo-E3, the most common isoform, enh ances neurite outgrowth. These effects are LRP mediated Although their role in the brain is not known with certainty, lipoproteins may maint ain cholesterol homeostasis in two ways. First, apo-E-containing lipop roteins may redistribute lipids by accepting cholesterol from cells wi th excess lipid and delivering the lipid to cells expressing lipoprote in receptors. Apo-AI-containing lipoproteins may also participate in t he removal of excess cholesterol from cells. Second, the lipid-enriche d apo-AI- and apo-E-containing lipoproteins, which are not taken up by lipoprotein receptors, would enter the CSF with the flow of the inter stitial fluid and pass into the venous circulation, thus removing exce ss cholesterol from the brain. (C)1997, Medikal Press.