Apolipoprotein E allelic influence on human cerebrospinal fluid apolipoproteins

Kathleen S. Montine, Casey N. Bassett, Joyce J. Ou, William R. Markesbery, Larry L. Swift, Thomas J. Montine

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33 Scopus citations

Abstract

The major apolipoproteins (apo) on human cerebrospinal fluid lipoproteins are apoA-I and apoE. Given the association between inheritance of the ε4 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.

Original languageEnglish (US)
Pages (from-to)2443-2451
Number of pages9
JournalJournal of Lipid Research
Volume39
Issue number12
Publication statusPublished - Dec 1 1998
Externally publishedYes

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Keywords

  • Alzheimer's disease
  • ApoA-I
  • ApoA-II
  • ApoE-ApoA-II heterodimer

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Montine, K. S., Bassett, C. N., Ou, J. J., Markesbery, W. R., Swift, L. L., & Montine, T. J. (1998). Apolipoprotein E allelic influence on human cerebrospinal fluid apolipoproteins. Journal of Lipid Research, 39(12), 2443-2451.