Specific recognition of the C-terminal end of Aβ42 by a high affinity monoclonal antibody

The neurotoxic peptide Aβ42 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 Aβ42 with high specificity. By this is meant that the paratope of the antibody must enclose the C-terminal end of Aβ42 including the carboxy-group of amino acid 42, and not just recognize a linear epitope in the C-terminal part of Aβ. 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 Aβ42. The generated Mab Aβ1.1 is indeed specific for the C-terminal end of Aβ42 to which it binds with high affinity. Mab Aβ1.1 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.