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J. Lipid Res.
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The Journal of Lipid Research, Vol. 39, 2443-2451, December 1998
Copyright © 1998 by Lipid Research, Inc.

Original Article

Apolipoprotein E allelic influence on human cerebrospinal fluid apolipoproteins

Kathleen S. Montinea, Casey N. Bassetta, Joyce J. Oua, William R. Markesberyd, Larry L. Swifta, and Thomas J. Montinea,b,c
a Departments of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232
b Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232
c Center for Molecular Neurosciences, Vanderbilt University Medical Center, Nashville, TN 37232
d Departments of Pathology, Neurology, and the Sanders-Brown Center on Aging, University of Kentucky Medical Center, Lexington, KY 40536

Correspondence to: Thomas J. Montine.

The major apolipoproteins (apo) on human cerebrospinal fluid lipoproteins are apoA-I and apoE. Given the association between inheritance of the {varepsilon}4 allele of the apoE gene (APOE4) and increased susceptibility to Alzheimer's disease, we tested the hypothesis that cerebrospinal fluid apolipoproteins may be influenced by APOE genotype and Alzheimer's disease. Lipoprotein fractions (d < 1.210 g/ml) were isolated from cerebrospinal fluid obtained from individuals with different APOE genotypes and with or without pathologically verified Alzheimer's disease. Apolipoproteins were separated by SDS-polyacrylamide gel electrophoresis and identified by silver nitrate staining, Western blotting, and N-terminal amino acid sequencing. Four protein species were detected by silver nitrate staining in subjects with an APOE3 allele: apoA-I, apoE monomer, apoE-apoA-II heterodimer, and apoE homodimer. In APOE4 homozygotes, only apoA-I and apoE monomer were detected. ApoA-II homodimer was demonstrated in all subjects by Western blotting. The relative levels of apoE- and apoA-II-containing apolipoproteins correlated with APOE genotype but were not altered by Alzheimer's disease. In contrast to apoE, no apoA-II immunoreactivity was observed with pathological structures in Alzheimer's disease brain.

These differences in cerebrospinal fluid apolipoproteins may influence lipoprotein trafficking and may be an element in the stratification of risk for Alzheimer's disease with APOE genotype.—Montine, K. S., C. N. Bassett, J. J. Ou, W. R. Markesbery, L. L. Swift, and T. J. Montine. Apolipoprotein E allelic influence on human cerebrospinal fluid apolipoproteins. J. Lipid Res. 1998. 39: 2443–2451.

Supplementary key words: ApoA-II, ApoE-ApoA-II heterodimer, apoA-I, Alzheimer's disease


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