Lipoprotein metabolism in brain has not yet been fully elucidated, although there are a few reports concerning lipids in the brain and lipoproteins and apolipoproteins in the cerebrospinal fluid (CSF). To establish normal levels of lipoproteins in human CSF, total cholesterol, phospholipids, and fatty acids as well as apolipoprotein E (apoE) and apoA-I levels were determined in CSF samples from 216 individuals. For particle characterization, lipoproteins from human CSF were isolated by affinity chromatography and analyzed for size, lipid and apolipoprotein composition. Two consecutive immunoaffinity columns with antibodies, first against apoE and subsequently against apoA-I, were used to define four distinct lipoprotein classes. The major lipoprotein fraction consisted of particles of 13-20 nm containing apoE and apoA-I as well as apoA-IV, apoD, apoH, and apoJ. In the second particle class (13-18 nm) mainly apoA-I and apoA-II but no apoE was detected. Third, there was a small number of large particles (18-22 nm) containing no apoA-I but apoE associated with apoA-IV, apoD, and apoJ. In the unbound fraction we detected small particles (10-12 nm) with low lipid content containing apoA-IV, apoD, apoH, and apoJ. In summary, we established lipid and apolipoprotein levels in CSF in a large group of individuals and described four distinct lipoprotein classes in human CSF, differing in their apolipoprotein pattern, lipid composition, and size. On the basis of our own data and previous findings from other groups, we propose a classification of CSF lipoproteins.-

Amyloid-beta (A beta) peptide, a major constituent of senile plaques and a hallmark of Alzheimer's disease (AD), is normally secreted by neurons and can be found in low concentrations in cerebrospinal fluid (CSF) and plasma where it is associated with lipoproteins. However, the physiological role of A beta secretion remains unknown. We measured the resistance to in vitro oxidation of CSF obtained from 20 control subjects and 30 patients with AD, and correlated it with CSF levels of antioxidants, lipids and A beta. We found that the oxidative resistance, expressed as a duration of the oxidation lag-phase, was directly related to CSF levels of A beta 1-40, A beta 1-42 and ascorbate and inversely to levels of fatty acids. These data suggest that, besides ascorbate, A beta is another major physiological antioxidant for CSF lipoproteins.

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Scavenger receptor class B type I (SR-BI) mediates the selective uptake of HDL cholesteryl esters (CEs) by the liver. LPL promotes this selective lipid uptake independent of lipolysis. In this study, the role of SR-BI in the mechanism of this LPL-mediated increase in selective CE uptake was explored. Baby hamster kidney (BHK) cells were transfected with the SR-BI cDNA, and significant SR-BI expression could be detected in immunoblots, whereas no SR-BI was visualized in control cells. Y1-BS1 murine adrenocortical cells were cultured without or with adrenocorticotropic hormone, and cells with no detectable or with SR-BI were obtained. These cells incubated without or with LPL in medium containing 125 I/[ 3 H]cholesteryl oleyl ether-labeled HDL 3 ; tetrahydrolipstatin inhibited the catalytic activity of LPL. In BHK and in Y1-BS1 cells without or with SR-BI expression, apparent HDL 3 selective CE uptake ([ 3 H]CEt ؊ 125 I) was detectable. Cellular SR-BI expression promoted HDL 3 selective CE uptake by ϳ 250-1,900%. In BHK or Y1-BS1 cells, LPL mediated an increase in apparent selective CE uptake. Quantitatively, this stimulating LPL effect was very similar in control cells and in cells with SR-BI expression. The uptake of radiolabeled HDL 3 was also investigated in human embryonal kidney 293 (HEK 293) cells that are an established SR-BI-deficient cell model. LPL stimulated [ 3 H]cholesteryl oleyl ether uptake from labeled HDL 3 by HEK 293 cells substantially, showing that LPL can induce selective CE uptake from HDL 3 independent of SR-BI. To explore the role of cell surface proteoglycans on lipoprotein uptake, we induced proteoglycan deficiency by heparinase treatment. Proteoglycan deficiency decreased the LPL-mediated promotion of HDL 3 selective CE uptake. In summary, evidence is presented that the stimulating effect of LPL on HDL 3 selective CE uptake is independent of SR-BI and lipolysis. However, cell surface proteoglycans are required for the LPL action on selective CE uptake. It is suggested that pathways distinct from SR-BI mediate selective CE uptake from HDL. -Rinninger, F., M. Brundert, I. Brosch, N. Donarski, R. M. Budzinski, and H. Greten. Lipoprotein lipase mediates an increase in selective uptake of HDL-associated cholesteryl esters by cells in culture independent of scavenger receptor BI.