Alzheimer's disease amyloid-beta peptide modulates apolipoprotein E isoform specific receptor binding.
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.
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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.
Martins
I J
IJ
Jeoung
M
M
Ji
T H
TH
Gandy
S E
SE
Martins
R N
RN
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000378:metabolism*; D001665:Binding Sites / Q000502:physiology; D018929:Cell Culture Techniques; D002460:Cell Line; D019281:Dimerization; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D012867:Skin / Q000166:cytology
D016229:Amyloid beta-Peptides; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E