Apolipoprotein E promotes the binding and uptake of β-amyloid into Chinese hamster ovary cells in an isoform-specific manner

D. S. Yang, D. H. Small, U. Seydel, J. D. Smith, J. Hallmayer, S. E. Gandy, R. N. Martins*

*Corresponding author for this work

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

The ε4 allele of apolipoprotein E gene is a major risk factor for Alzheimer's disease. However, the mechanism by which the E4 isoform of apolipoprotein E increases the risk of Alzheimer's disease is poorly understood. To determine whether the isoform-specific effects of apolipoprotein E may be mediated via clearance of bound β-amyloid, we examined the uptake of β-amyloid 1-40 into Chinese hamster ovary cells in the presence or absence of the apolipoprotein E isoforms E2, E3 and E4. Apolipoprotein E2 and E3 treatments were associated with higher association of β-amyloid with cells as compared to treatment with E4. Heparin blocked the association of β-amyloid with cells, as did an antibody to one of the apolipoprotein E receptors (the low-density lipoprotein receptor-related protein). Thus, the apolipoproteins E2 and E3, but not E4, may play important roles in the clearance of β-amyloid from the extracellular space via the low-density lipoprotein receptor-related protein.

Original languageEnglish
Pages (from-to)1217-1226
Number of pages10
JournalNeuroscience
Volume90
Issue number4
DOIs
Publication statusPublished - Jun 1999
Externally publishedYes

Keywords

  • β-amyloid
  • Alzheimer's disease
  • Apolipoprotein E
  • Chinese hamster ovary cells
  • Heparan sulphate proteoglycans
  • LDL receptor- related protein

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