Apolipoprotein E associated with reconstituted high-density lipoprotein-like particles is protected from aggregation.
Ellen Hubin1,2,3, Philip B Verghese4, Nico van Nuland2,3
1Nanobiophysics Group, Technical Medical Centre, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.
FEBS Letters
|May 7, 2019
Summary
Lipid-free Apolipoprotein E (APOE) aggregates in solution, with lipidation preventing this aggregation. This finding is crucial for understanding Alzheimer's disease (AD) risk associated with APOE genotype.
Area of Science:
- Biochemistry
- Neuroscience
- Molecular Biology
Background:
- Apolipoprotein E (APOE) genotype is a key determinant of Alzheimer's disease (AD) susceptibility.
- The APOE ε4 allele is a significant risk factor for late-onset AD.
- ApoE lipidation status is implicated in amyloid-beta (Aβ) peptide metabolism, but the mechanisms are unclear.
Purpose of the Study:
- To investigate the biophysical behavior of different Apolipoprotein E (APOE) isoforms.
- To elucidate the impact of lipidation on APOE structure and aggregation.
Main Methods:
- Preparation of lipid-free and lipid-bound ApoE particles for all three isoforms (ApoE2, ApoE3, ApoE4).
- Biophysical characterization of these particles under near-physiological conditions.
Main Results:
- Lipid-free ApoE exhibits isoform-dependent aggregation in vitro.
- Lipidation of ApoE significantly impedes this aggregation process.
- This suggests a protective role for lipid-bound ApoE.
Conclusions:
- Lipidation is critical for maintaining ApoE stability and preventing aggregation.
- Understanding ApoE lipidation may offer new insights into AD pathogenesis and therapeutic strategies.
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