Alzheimer's Disease Amyloid-beta Peptide Modulates Apolipoprotein E Isoforms Specific Receptor Binding
Document Type
Journal Article
Publisher
IOS Press
Faculty
Faculty of Computing, Health and Science
School
School of Exercise, Biomedical and Health Science
RAS ID
2759
Abstract
The major protein component of the extracellular deposits in Alzheimer's disease (AD) is a 4 kDa peptide termed amyloid-β (Aβ). This peptide is known to bind apolipoprotein E (apoE), a key mediator of lipoprotein transport, in an isoform specific manner. Whilst these isoform specific effects on apoE are well recognized, the functional significance of this interaction is poorly understood. Here, we investigated the influence of Aβ on apoE-mediated lipoprotein binding to cells using fluorescently tagged lipoprotein-like emulsions. Using this approach, we demonstrate that Aβ enhanced the normally poor binding of apoE2 lipoprotein-like particles to fibroblasts in culture, whilst markedly reducing the binding of apoE3 and apoE4. This suggests that the action of apoE isoforms on cellular lipoprotein or cholesterol metabolism is differentially modulated by Aβ. This also suggests that Aβ may also compromise apoE function in the Alzheimer disease affected brain.
DOI
10.3233/JAD-2005-7406
Comments
Hone, E. , Martins, I. J., Jeoung, M., Ji, T., Gandy, S. , & Martins, R. N. (2005). Alzheimer's disease amyloid-beta peptide modulates apolipoprotein E isoforms specific receptor binding. Journal of Alzheimer's Disease, 7(4), 303-314. Available here