Apolipoproteins in human cerebrospinal fluid.

Abstract

The presence of apolipoproteins A-I, E, C-II, and GIII and the absence of apolipoprotein B was demonstrated in human cerebrospinal fluid. The concentration of apolipoproteins was measured by electroimmunoassay. Apolipoproteins E, C-I1, and C-Il were present in cerebrospinal fluid at 3-5% of their concentration in plasma; the cerebrospinal fluid level of apolipoprotein A-I was 0.4%. Most of the cerebrospinal fluid apolipoproteins were present in the p < 1.21 g/ml i protein fraction. The major apoli proteins of cerebrospinal fluid are E and A-I. The possible mechanism of transfer and the physiological and pathophysiological role of apolipoproteins in cerebrospinal fluid are postulated.Lipoproteins are macromolecular complexes with Mrs ranging from 107 for very low density lipoproteins (VLDL), 2-3 X 106 for low density lipoproteins (LDL), and 2-4 X 105 for high density lipoproteins (HDL) (1, 2). The protein moieties of the lipoproteins, the apolipoproteins (apo), have specific physiological functions, and some of their alterations are associated with pathological conditions (1-3). The enzyme lecithin cholesteryl acyltransferase requires the presence, as a cofactor, of apo A-I which has a Mr of 28,000 (1, 2). Recently, a cholesteryl ester transfer protein has been described and it is thought to be one of the minor apos, apo D (Mr, 22,000) (4). The action of lipoprotein lipase is modulated by the apo Cs which have Mrs of approximately 000 (1, 2). Cellular cholesterol metabolism is regulated by apo B (Mr, 260,000) and apo E (Mr) 33,000) (1, 2,5, 6).Because interstitial fluid is in direct contact with the cell, knowledge of its apo composition and concentration is important in understanding the regulation of cellular lipid metabolism. Lipoprotein and apo profiles of plasma are being extensively investigated, but information on the apo composition of interstitial fluid is sparse. Apo B concentration in human peripheral lymph is 10% of its concentration in plasma (7) and it is biologically active at that concentration (8). It has been postulated that apos are present in the circulation not only as part of the lipoprotein particle but also as "free" apos-i.e., not associated with a conventional lipoprotein particle (9). Studies with rat renal lymph have shown that its apo composition is different from that in plasma but it is similar to the apo composition of the lipoprotein-free p > 1.21 g/ml fraction (10).The dominant process in the formation of interstitial fluid is filtration of plasma. The concentrations of macromolecules in the interstitial fluids, lymph, and cerebrospinal fluid are inversely related to their Mr (11). Because the permeability of the blood cerebrospinal fluid barrier is much more restricted than the permeability of peripheral capillaries, we chose to examine whether apos are present in cerebrospinal fluid as an approach to the molecular form in which apos are transferred. METHODSCerebrospinal fluid was collected from patients undergoing myelography. Unconcentrated fluid was used for determi...

Novel Large Apolipoprotein E‐Containing Lipoproteins of Density 1.006–1.060 g/ml in Human Cerebrospinal Fluid

“…The diameters of previously identified CSF lipoproteins were 11-13 nm according to Roheim et al (1979) and averaged 13.9 nm according to Pitas et al (1987). In unfractionated CSF we confirmed these observations, demonstrating that the bulk of CSF lipoproteins have sizes (11.6 ±2.2 nm) similar to those of most plasma HDL.…”

“…The major CSF apolipoproteins are apoE and apolipoprotein A-I (apoA-I), whereas apolipoprotein B (apoB), which is abundant in blood plasma, is absent from CSF (Roheim et al, 1979). CSF apoE originates in the CNS, whereas plasma apoE is largely produced by the liver (Linton et al, 1991).…”

Nascent Astrocyte Particles Differ from Lipoproteins in CSF

“…For CSF fractions (see Fig. 3A and B), the areas of the apoprotein curves were adjusted to reflect the relative apoprotein concentration in total CSF, where apoE -2.9-5.9~.tg/ml (Pitas et al, 1987b;Caisson et al, 1991;Blennow et al, 1994;Lehtimaki et al, 1995), apoAl -4.5 ptg/ml (Roheim et al, 1979;Rifai et al, 1986), apoJ -2.4 g/ml (Choi-Miura et al, 1992), and apoAll -0.5 ,ug/ml (W. Rebeck, personal communication). For astrocyte media fractions (see Fig.…”

“…CSF is produced by the choroid plexus and also contains nonresorbed products derived from the interstitial space of the brain and, to a smaller degree, plasma. Studies have shown that several apolipoproteins are present in the CSF, with the two most abundant being apoE and apoAl (Roheim et al, 1979;Pitas et al, l987b). These proteins appear to reside in distinct lipoprotein particles that are HDLlike in density as determined by gradient centrifugation (Pitas et al, 1987b).…”

Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-β

“…In the plasma, apoE is present in a variety of types of lipoproteins such as large very low-density lipoproteins (VLDL) as well as high-density lipoproteins (HDL). In the cerebrospinal fluid (CSF), apoE is only present in lipoproteins that are HDL-like in size (Borghini et al, 1995;LaDu et al, 1998;Pitas et al, 1987b;Roheim et al, 1979). Interestingly, apoE-containing lipoproteins in the CSF are produced predominantly, if not exclusively, by cells within the CNS (Linton et al, 1991).…”