Characterization of conformation-specific antibodies TOMA-1 and TTCM-1 for recombinant tau monomer and amplified brain derived tau oligomer

Abstract

Tauopathies are a set of neurodegenerative diseases characterized by the pathological accumulation of aggregated tau in the brain. Recent breakthrough evidence has revealed the existence of different strains of tau oligomer (TauO) which direct the different pathological presentation of individual tauopathies. Extensive research efforts have been devoted to search for specific antibodies or drug candidates which target TauO to serve as promising alternatives to treat Alzheimer's disease (AD) in future. To screen for the antibodies which are able to bind with amplified brain derived tau oligomer (aBDTO), we have investigated the binding parameters of the tau oligomer-specific monoclonal antibody-1 (TOMA-1) and toxic tau conformation-specific monoclonal antibody-1 (TTCM-1) with the recombinant tau monomer (rTauM) and aBDTO using isothermal titration calorimetry (ITC). TOMA-1 specifically recognizes the amino acid sequences 367–386, 382–401 and 367–386 and TTCM-1 specifically recognizes the amino acid sequence 307–326 of rTauM and aBDTO, respectively. Our results demonstrated that both TOMA-1 and TTCM-1 have a high binding affinity with aBDTO compared to rTauM. We also observed that higher the binding affinity of the antibody to the aBDTO, lower was the toxicity of the aBDTO and vice versa. Our study taken together presents both TOMA-1 and TTCM-1 to be potential immunotherapeutic agents against AD.