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

FEBS Letters

article

Ellen Hubin¹  Philip B. Verghese⁴  Nico van Nuland²  Kerensa Broersen¹ 

[1] Nanobiophysics Group, Technical Medical Centre, Faculty of Science and Technology, University of Twente;Department of Biotechnology (DBIT), Vrije Universiteit Brussel (VUB);Structural Biology Research Center;Department of Neurology, Washington University School of Medicine

关键词: aggregation;    Alzheimer’s disease;    apolipoprotein E;    highdensity lipoprotein;    isoform;    lipidation;   

DOI  :  10.1002/1873-3468.13428

来源: John Wiley & Sons Ltd.

【 摘 要 】

Apolipoprotein E (APOE) genotype determines Alzheimer’s disease (AD) susceptibility, with the APOE e4 allele being an established risk factor for lateonset AD. The ApoE lipidation status has been reported to impact amyloidbeta (Ab) 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.

【 授权许可】

Unknown