Apolipoprotein E associated with reconstituted high-density lipoprotein-like particles is protected from aggregation

Ellen Hubin, Philip B. Verghese, Nico van Nuland, Kerensa Broersen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
24 Downloads (Pure)

Abstract

Apolipoprotein E (APOE) genotype determines Alzheimer's disease (AD) susceptibility, with the APOE ε4 allele being an established risk factor for late-onset AD. The ApoE lipidation status has been reported to impact amyloid-beta (Aβ) peptide metabolism. The details of how lipidation affects ApoE behavior remain to be elucidated. In this study, we prepared lipid-free and lipid-bound ApoE particles, mimicking the high-density lipoprotein particles found in vivo, for all three isoforms (ApoE2, ApoE3, and ApoE4) and biophysically characterized them. We find that lipid-free ApoE in solution has the tendency to aggregate in vitro in an isoform-dependent manner under near-physiological conditions and that aggregation is impeded by lipidation of ApoE.

Original languageEnglish
Pages (from-to)1144-1153
Number of pages10
JournalFEBS letters
Volume593
Issue number11
Early online date6 May 2019
DOIs
Publication statusPublished - 1 Jun 2019

    Fingerprint

Keywords

  • UT-Hybrid-D
  • Alzheimer's disease
  • apolipoprotein E
  • high-density lipoprotein
  • isoform
  • lipidation
  • aggregation

Cite this