Apolipoprotein E associated with reconstituted high‐density lipoprotein‐like particles is protected from aggregation. Issue 11 (27th May 2019)

• Record Type: Journal Article
• Authors: Hubin, Ellen; Verghese, Philip B.; van Nuland, Nico; Broersen, Kerensa
• Is Part Of: FEBS letters. Volume 593:Issue 11(2019)
• Page Start: 1144
• Page End: 1153
• Publication Date: 2019-05-27
• Subjects: aggregation -- Alzheimer's disease -- apolipoprotein E -- high‐density lipoprotein -- isoform -- lipidation; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13428
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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.