title: Specific recognition of the C-terminal end of A beta 42 by a high affinity monoclonal antibody.
abstract: The neurotoxic peptide A beta(42) is derived from the amyloid precursor protein by proteolytic cleavage and is deposited in the brain of patients suffering from Alzheimer's disease (AD). In this study we generate a high affinity monoclonal antibody that targets the C-terminal end of A beta(42) with high specificity. By this is meant that the paratope of the antibody must enclose the C-terminal end of A beta(42) including the carboxy-group of amino acid 42, and not just recognize a linear epitope in the C-terminal part of A beta. This has been accomplished by using a unique antigen construct made by the Ligand Presenting Assembly technology (LPA technology). This strategy results in dimeric presentation of the free C-terminal end of A beta(42). The generated Mab A beta1.1 is indeed specific for the C-terminal end of A beta(42) to which it binds with high affinity. Mab A beta1.1 recognizes the epitope in human AD tissue and stains plaques with high specificity. Therefore the monoclonal antibody can thus be useful in the histological investigations of the AD pathology.
authors.affiliation: Clinical Institute, The Faculty of Health Science, Aarhus University, Brendstrupgårdsvej 100, 8200 Arhus N, Denmark. trine@loke.dk
authors.forename: Trine Veje
authors.initials: TV
authors.lastname: Axelsen
authors.forename: Arne
authors.initials: A
authors.lastname: Holm
authors.forename: Svend
authors.initials: S
authors.lastname: Birkelund
authors.forename: Gunna
authors.initials: G
authors.lastname: Christiansen
authors.forename: Michael
authors.initials: M
authors.lastname: Ploug
authors.forename: Ida Elisabeth
authors.initials: IE
authors.lastname: Holm
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D055503:Protein Multimerization
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)