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

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

doi:10.1002/1873-3468.13428

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 journal › Article › Academic › peer-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 language	English
Pages (from-to)	1144-1153
Number of pages	10
Journal	FEBS letters
Volume	593
Issue number	11
Early online date	6 May 2019
DOIs	https://doi.org/10.1002/1873-3468.13428
Publication status	Published - 1 Jun 2019

Keywords

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

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Hubin_et_al-2019-FEBS_LettersFinal published version, 936 KBLicence: CC BY

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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.",

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AU - Broersen, Kerensa

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

Abstract

Keywords

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