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

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

Research output: Contribution to journalArticleAcademicpeer-review

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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

Apolipoproteins E
HDL Lipoproteins
Agglomeration
Apolipoprotein E4
Lipids
Alzheimer Disease
Protein Isoforms
Apolipoprotein E2
Apolipoprotein E3
Amyloid beta-Peptides
Disease Susceptibility
Amyloid
Metabolism
Alleles
Genotype
Peptides

Keywords

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

Cite this

Hubin, Ellen ; Verghese, Philip B. ; van Nuland, Nico ; Broersen, Kerensa. / Apolipoprotein E associated with reconstituted high-density lipoprotein-like particles is protected from aggregation. In: FEBS letters. 2019 ; Vol. 593, No. 11. pp. 1144-1153.
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Apolipoprotein E associated with reconstituted high-density lipoprotein-like particles is protected from aggregation. / Hubin, Ellen; Verghese, Philip B.; van Nuland, Nico; Broersen, Kerensa.

In: FEBS letters, Vol. 593, No. 11, 01.06.2019, p. 1144-1153.

Research output: Contribution to journalArticleAcademicpeer-review

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