Specific recognition of the C-terminal end of A beta 42 by a high affinity monoclonal antibody

Mol Immunol. 2009 Jul;46(11-12):2267-73. doi: 10.1016/j.molimm.2009.04.007. Epub 2009 May 17.

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.

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / immunology
  • Amyloid beta-Peptides / metabolism*
  • Antibodies, Monoclonal / immunology*
  • Antibody Affinity
  • Brain / metabolism
  • Brain / pathology
  • Humans
  • Immunohistochemistry
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism*
  • Protein Multimerization

Substances

  • Amyloid beta-Peptides
  • Antibodies, Monoclonal
  • Peptide Fragments
  • amyloid beta-protein (1-42)