Hyman, Bradley T

Publication Detail

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Alzheimer's disease amyloid-beta peptide modulates apolipoprotein E isoform specific receptor binding.

E Hone; I J Martins; M Jeoung; T H Ji; S E Gandy; R N Martins (Profiled Author: Gandy, Samuel E)

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.
Journal of Alzheimer's disease : JAD 2005;7(4):303-14.

The major protein component of the extracellular deposits in Alzheimer's disease (AD) is a 4 kDa peptide termed amyloid-beta (Abeta). 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 Abeta on apoE-mediated lipoprotein binding to cells using fluorescently tagged lipoprotein-like emulsions. Using this approach, we demonstrate that Abeta 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 Abeta. This also suggests that Abeta may also compromise apoE function in the Alzheimer disease affected brain.

2 Originating Grant

• 1.

  Gandy, Samuel E

  Interdisciplinary Approach to Alzheimer Drug Discovery

  30 September 1991 - 31 August 2010

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 11,063,275

• 2.

  GREENGARD, PAUL

  INTERDISCIPLINARY APPROACH TO ALZHEIMER DRUG DISCOVERY

  30 September 1991 - 31 July 1996

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 2,198,300

Scientific Context

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