title: Isoform-specific interactions of human apolipoprotein E to an intermediate conformation of human Alzheimer amyloid-beta peptide.
abstract: Brain plaque deposits of amyloid-beta peptide (Abeta) is a pathological hallmark of Alzheimer's disease (AD) and apolipoprotein E (apoE) is thought to be involved in its deposition. One hypothesis for the role of apoE in the pathogenesis of AD is that apoE may be involved in deposition or clearance of Abeta by direct protein-to-protein interaction. Lipidated apoE4 bound preferentially to an intermediate aggregated form of Abeta and formed two- to three-fold more binding complexes than isoforms apoE2 or apoE3. The interaction was detected by a sandwich ELISA with capture antibodies specific for the N-terminus of apoE, whereas the interaction was not recognized with a C-terminal antibody. The observations indicate that the C-terminus of apoE4 interacts with the intermediate form of Abeta. The differential risk of AD related to apoE genotype may be the result of an enhanced capacity of apoE4 binding to an intermediate aggregated form of Abeta.
authors.affiliation: Neurobiology, Pfizer Inc., Kalamazoo, MI 49001, USA.
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Stratman
authors.forename: Christine K
authors.initials: CK
authors.lastname: Castle
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Taylor
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Epps
authors.forename: George W
authors.initials: GW
authors.lastname: Melchior
authors.forename: Donald B
authors.initials: DB
authors.lastname: Carter
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry; D017434:Protein Structure, Tertiary
chemical_list: D016229:Amyloid beta-Peptides; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; D020033:Protein Isoforms; C078592:amyloid beta-protein (1-40)