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Address correspondence to Minoru Tozuka, Ph.D., Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan; tel 81 263 37 2805; fax 81 263 34 5316; e-mail: mtozuka{at}hsp.md.shinshu-u.ac.jp.
Apolipoprotein (apo) J, abundant in cerebrospinal fluid (CSF), is known to play a role in the pathogenesis of Alzheimers disease (AD); however, the mechanism remains obscure. To characterize the apoJ-containing lipoproteins in CSF, we compared the distribution of apoJ in CSF lipoprotein particles with those of apoE and apoAI. CSF lipoproteins (fractionated by ultracentrifugation, gel-filtration chromatography, and agarose-gel electrophoresis) were characterized by immunoblot analysis using anti-apoJ, anti-apoE, and anti-apoAI antibodies. Immunoprecipitation and immunoabsorption were used to clarify the combinations in which these apolipoproteins exist. All of the apoJ in CSF was in the fraction with density of
1.250 g/ml after ultracentrifugation; relatively little apoE and apoAI was in that fraction. In gel-filtration chromatography, the main peak of apoJ-containing lipoprotein particles was clearly distinguishable from those of apoE- and apoAI-containing lipoproteins. Immunoabsorption and agarose-gel electrophoresis indicated that the dominant apoJ-containing lipoprotein particles did not contain apoE. These findings indicate that a significant fraction of the apoJ present in CSF does not co-exist with apoE or apoAI within the same particles. Immunoprecipitation revealed two types of particles: one that contains no apoAI but apoE and another that contains no apoE but apoAI. These results show that several subfractions of lipoprotein particles exist in CSF, differing from each other in their combinations of apoE, apoJ, and apoAI. We concluded that there are at least 9 forms or combinations (including free apolipoproteins) of apoJ, apoE, and apoA1 in the CSF.
Keywords: apolipoprotein J, cerebrospinal fluid, lipoprotein particles, Alzheimers disease
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