Specific recognition of the C-terminal end of A beta 42 by a high affinity monoclonal antibody.
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.
Axelsen
Trine Veje
TV
Clinical Institute, The Faculty of Health Science, Aarhus University, Brendstrupgårdsvej 100, 8200 Arhus N, Denmark. trine@loke.dk
Holm
Arne
A
Birkelund
Svend
S
Christiansen
Gunna
G
Ploug
Michael
M
Holm
Ida Elisabeth
IE
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
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)