Title

Alzheimer's Disease Amyloid-beta Peptide Modulates Apolipoprotein E Isoforms Specific Receptor Binding

Document Type

Journal Article

Publisher

IOS Press

Faculty

Computing, Health and Science

School

Exercise, Biomedical and Health Science

RAS ID

2759

Comments

This article was originally published as: 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. Original article available here

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.