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Apolipoprotein E associated with reconstituted high‐density lipoprotein‐like particles is protected from aggregation
Author(s) -
Hubin Ellen,
Verghese Philip B.,
Nuland Nico,
Broersen Kerensa
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13428
Subject(s) - apolipoprotein e , lipid anchored protein , lipoprotein , gene isoform , apolipoprotein b , chemistry , lipoprotein particle , lipid metabolism , in vitro , biochemistry , microbiology and biotechnology , biology , biophysics , cholesterol , medicine , very low density lipoprotein , autophagy , disease , gene , apoptosis
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.