title: Apolipoprotein E promotes the binding and uptake of beta-amyloid into Chinese hamster ovary cells in an isoform-specific manner.
abstract: 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.
authors.affiliation: Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, University of Western Australia, Perth, Australia.
authors.forename: D S
authors.initials: DS
authors.lastname: Yang
authors.forename: D H
authors.initials: DH
authors.lastname: Small
authors.forename: U
authors.initials: U
authors.lastname: Seydel
authors.forename: J D
authors.initials: JD
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Hallmayer
authors.forename: S E
authors.initials: SE
authors.lastname: Gandy
authors.forename: R N
authors.initials: RN
authors.lastname: Martins
mesh_terms: 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
chemical_list: 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