Alz-50 and MC-1, a new monoclonal antibody raised to paired helical filaments, recognize conformational epitopes on recombinant tau

Using a series of recombinant tau and FAC1 mutant proteins, this study demonstrates by Western and dot blot analysis that 1) shared epitopes between tan and FAC1 are responsible for Alz-50 binding; 2) Alz-50 reactivity is dependent on two discontinuous portions of the tau molecule; 3) Alz-50 reactivity is most likely the result of a conformational alteration of tan monomers in Alzheimer's disease; and 4) the epitope for MC-1, a novel monoclonal antibody, maps to similar regions of tau but does not react with FAC1. These data raise questions regarding previous studies which have suggested that tau lacks a specific conformation and illustrate the utility of the Alz-50 and MC-1 antibodies in recognizing a distinct pathological conformation of the tau molecule in Alzheimer's disease.