Apolipoprotein E promotes the binding and uptake of beta-amyloid into Chinese hamster ovary cells in an isoform-specific manner.
The epsilon4 allele of apolipoprotein E gene is a major risk factor for Alzheimer's disease. However, the mechanism by which the E4 isoform of apolipoprotein E increases the risk of Alzheimer's disease is poorly understood. To determine whether the isoform-specific effects of apolipoprotein E may be mediated via clearance of bound beta-amyloid, we examined the uptake of beta-amyloid 1-40 into Chinese hamster ovary cells in the presence or absence of the apolipoprotein E isoforms E2, E3 and E4. Apolipoprotein E2 and E3 treatments were associated with higher association of beta-amyloid with cells as compared to treatment with E4. Heparin blocked the association of beta-amyloid with cells, as did an antibody to one of the apolipoprotein E receptors (the low-density lipoprotein receptor-related protein). Thus, the apolipoproteins E2 and E3, but not E4, may play important roles in the clearance of beta-amyloid from the extracellular space via the low-density lipoprotein receptor-related protein.
Yang
D S
DS
Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, University of Western Australia, Perth, Australia.
Small
D H
DH
Seydel
U
U
Smith
J D
JD
Hallmayer
J
J
Gandy
S E
SE
Martins
R N
RN
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000494:pharmacology*; D016466:CHO Cells / Q000378:metabolism*; D006224:Cricetinae; D006493:Heparin / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics; D011973:Receptors, LDL / Q000276:immunology
D016229:Amyloid beta-Peptides; D000906:Antibodies; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; D011973:Receptors, LDL; C078592:amyloid beta-protein (1-40); D006493:Heparin