STRUCTURE AND FUNCTIONS OF HUMAN CEREBROSPINAL-FLUID LIPOPROTEINS FROM INDIVIDUALS OF DIFFERENT APOE GENOTYPES

Recent data have implicated apolipoprotein E (apoE) in neuritic outgro wth, synaptic stability, and Alzheimer's disease; these data led us to examine the normal role of apoE-containing lipoproteins in the centra l nervous system (CNS). We isolated lipoproteins from human cerebrospi nal fluid (CSF) in order to examine their composition and potential fu nctions. CSF particles were composed of approximately one-third protei n, one-third phospholipid, and one-third cholesterol. ApoE3 formed hom odimers and heterodimers with apoA-II, while apoE4, as expected, was m onomeric. We addressed the function of CSF lipoproteins with assays of cholesterol efflux and cholesterol influx. CSF lipoproteins decreased intracellular levels of cholesterol in cholesterol-loaded fibroblasts , suggesting these particles can act to remove excess lipids from cell s. CSF Lipoproteins competed for (125) I-labeled LDL degradation by fi broblasts, suggesting they can also interact with the LDL receptor. Fu rthermore, CSF lipoproteins labeled with the fluorescent dye Dil were internalized by neuroglioma cells and primary neurons and astrocytes i n culture. Together, these data support a model of CSF Lipoproteins ac ting to remove lipids from degenerating cells and delivering lipids to cells for new membrane synthesis or storage. (C) 1998 Academic Press.