Characterization of apolipoprotein E-containing lipoproteins in cerebrospinal fluid: Effect of phenotype on the distribution of apolipoprotein E

Background: Apolipoprotein (apo) E, one of the main apolipoproteins in the central nervous system, may play an important role in lipid metabolism; how ever, the details of its function are poorly understood. In this study, we characterized apoE-containing lipoproteins in cerebrospinal fluid (CSF) and examined the effect of apoE phenotype on the distribution of apoE among th e lipoprotein fractions. Methods: CSF lipoproteins were fractionated by gel filtration and ultracent rifugation, and then characterized by electrophoresis, immunoblot, electron microscopy, and analysis of apoE, total cholesterol, and phospholipid conc entrations. Results: The ratio of sialylated to nonsialylated apoE was higher in CSF th an in serum. However, the fundamental forms containing apoE homodimers or h eterodimers [such as apo(E-AII) and apo(AII-E2AII) complexes] were similar in CSF and serum. apoE-containing lipoproteins were fractionated at densiti es of <1.006, 1.063-1.125, and 1.125-1.21 kg/L. Neither apoE nor apoAI was detected in the fraction with a density range of 1.006-1.063 kg/L. The diam eters of the lipoprotein particles with densities of <1.006, 1.063-1.125, a nd 1.125-1.21 kg/L were 16.7 +/- 3.1, 14.0 +/- 3.5 and 11.6 +/- 2.8 nm (mea n +/- SD, n = 200), respectively. All of these lipoproteins exhibited a sph erical structure. The distribution profile of apoE-containing lipoproteins was affected by the apoE phenotype. A relatively large amount of apoE-conta ining lipoproteins was isolated from the fraction with a density >1.125 kg/ L obtained from CSF associated with apoE2 or apoE3. This tendency was more obvious in CSF associated with apoE2 than in CSF without apoE2. apoE-contai ning lipoproteins were predominantly observed in the fraction with a densit y of <1.006 kg/L obtained from CSF associated with apoE4. Conclusions: The lipoproteins in CSF have a unique composition that is diff erent from that of the lipoproteins in plasma. However, the differences in diameter between the CSF fractions were not as lai ge as for the serum frac tions. Our data suggest that the apoE phenotype may affect the distribution profile of apoE-containing lipoproteins in the CSF. This would mean that t he metabolism of apoE-containing lipoproteins depends on the apoE isoform p resent. (C) 1999 American Association for Clinical Chemistry.