Characterization of four lipoprotein classes in human cerebrospinal fluid

Abstract

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.-

Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity

“…The role of lipoproteins in human CNS is still not completely elucidated; however, several studies have suggested a role of oxidized lipoproteins in the development of neurogenerative diseases. 10 Lipoproteins exist in the CNS and surrounding vasculature, 35 and it has been demonstrated that astrocytes synthesize HDL-like lipoproteins and apoproteins. 36 Uptake and transport of lipoproteins (HDL and LDL) from plasma through the blood Á/brain barrier (BBB) have been demonstrated in normal conditions.…”

Perspectives of Microscopy Methods for Morphology Characterisation of Extracellular Vesicles from Human Biofluids

“…The stationary phase allows smaller particles such as proteins to enter the pores and traverse a longer path until elution, while the particles that are too big to access the pores travel faster and elute right after the void volume of the column [28,39]. The most apparent limitation regarding the SEC isolation of EVs is its inability to separate EVs from other particles of similar size, including lipoproteins and chylomicrons [39,40]. However, SEC does not seem to compromise the integrity and functionality of isolated EVs like other commonly used EV isolation methods [28,36,41,42].…”

“…The use of phosphate buffer (PBS) as a mobile phase during EV separation by SEC can form crystals or spherical bubbles of similar size as EVs (Figure 3A,B). In addition, protein aggregates or lipoproteins [40] of size similar to EVs can be co-isolated in the EV fractions (Figure 3C,D). They are darker (more electron opaque) and without membranes, but especially hard to be distinguished from EVs when using conventional EM techniques with staining and possible collapse of the membrane during the sample preparation.…”

Neurotrophins as Key Regulators of Cell Metabolism: Implications for Cholesterol Homeostasis

“…In particular, ABCA1, ABCG1 and ABCG4 isoforms mediate cholesterol efflux from neurons to lipid-free apoA1 and High-Density Lipoprotein (HDL) particles [ 231 ]. Subsequently, secreted cholesterol-rich particles are released into the cerebrospinal fluid [ 232 , 233 , 234 ]. These lipoproteins also enter the systemic bloodstream by interacting with specific receptors such as LRP1 and scavenger receptor class B type I (SR-BI), both expressed in endothelial cells of brain capillaries [ 235 , 236 ].…”