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...