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1
Central Clinical Laboratories, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
2
Department of Functional Polymer Science, Faculty of
Textile Science and Technology, Shinshu University, 3-15-1 Tokita, Ueda
386-0018, Japan.
3
Department of Laboratory Medicine, Shinshu University
School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
a Author for correspondence. Fax 81-263-34-5316; e-mail mtozuka{at}hsp.md.shinshu-u.ac.jp
Background: Apolipoprotein (apo) E, one of the main apolipoproteins in the central nervous system, may play an important role in lipid metabolism; however, 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 the lipoprotein fractions.
Methods: CSF lipoproteins were fractionated by gel filtration and ultracentrifugation, and then characterized by electrophoresis, immunoblot, electron microscopy, and analysis of apoE, total cholesterol, and phospholipid concentrations.
Results: The ratio of sialylated to nonsialylated apoE was higher in CSF than in serum. However, the fundamental forms containing apoE homodimers or heterodimers [such as apo(E-AII) and apo(AII-E2-AII) complexes] were similar in CSF and serum. apoE-containing lipoproteins were fractionated at densities 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 diameters of the lipoprotein particles with densities of <1.006, 1.063–1.125, and 1.125–1.21 kg/L were 16.7 ± 3.1, 14.0 ± 3.2, and 11.6 ± 2.8 nm (mean ± SD, n = 200), respectively. All of these lipoproteins exhibited a spherical structure. The distribution profile of apoE-containing lipoproteins was affected by the apoE phenotype. A relatively large amount of apoE-containing 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-containing lipoproteins were predominantly observed in the fraction with a density of <1.006 kg/L obtained from CSF associated with apoE4.
Conclusions: The lipoproteins in CSF have a unique composition that is different from that of the lipoproteins in plasma. However, the differences in diameter between the CSF fractions were not as large as for the serum fractions. Our data suggest that the apoE phenotype may affect the distribution profile of apoE-containing lipoproteins in the CSF. This would mean that the metabolism of apoE-containing lipoproteins depends on the apoE isoform present.
The following articles in journals at HighWire Press have cited this article:
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  I. Dolev and D. M. Michaelson A nontransgenic mouse model shows inducible amyloid-{beta} (A{beta}) peptide deposition and elucidates the role of apolipoprotein E in the amyloid cascade PNAS, September 21, 2004; 101(38): 13909 - 13914. [Abstract] [Full Text] [PDF]
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 N. Demeester, G. Castro, C. Desrumaux, C. De Geitere, J. C. Fruchart, P. Santens, E. Mulleners, S. Engelborghs, P. P. De Deyn, J. Vandekerckhove, et al. Characterization and functional studies of lipoproteins, lipid transfer proteins, and lecithin:cholesterol acyltransferase in CSF of normal individuals and patients with Alzheimer's disease J. Lipid Res., June 1, 2000; 41(6): 963 - 974. [Abstract] [Full Text]
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