Affiliations: [a] The Sir James McCusker Alzheimer's Disease Research Unit, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, C/- Hollywood Private Hospital, 115 Monash Avenue, Nedlands WA 6009, Australia | [b] School of Psychiatry and Clinical Neurosciences, The University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009, Australia | [c] Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107-5587, USA | [d] Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA
Correspondence:
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Corresponding author: Prof. R.N. Martins, The Sir James McCusker Alzheimer's Disease Research Unit, School of Exercise, Biomedical of Health Sciences, Edith Cowan University, C/- Hollywood Private Hospital, 115 Monash Avenue, Nedlands WA 6009, Australia. Tel.: +61 8 9346 6656; Fax: +61 8 9346 6666; E-mail: [email protected].
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.
Keywords: Amyloid-β, Alzheimer's disease, apolipoprotein E, periphery, cholesterol, lipoproteins
