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FEBS Lett. 2019 Jun;593(11):1144-1153. doi: 10.1002/1873-3468.13428. Epub 2019 May 27.

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

Author information

1
Nanobiophysics Group, Technical Medical Centre, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.
2
Structural Biology Brussels, Department of Biotechnology (DBIT), Vrije Universiteit Brussel (VUB), Belgium.
3
Structural Biology Research Center, VIB, Brussels, Belgium.
4
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
5
Applied Stem Cell Technologies, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.

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.

KEYWORDS:

Alzheimer's disease; aggregation; apolipoprotein E; high-density lipoprotein; isoform; lipidation

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