THE STRUCTURAL BASIS OF MONOCLONAL-ANTIBODY ALZ50S SELECTIVITY FOR ALZHEIMERS-DISEASE PATHOLOGY

The epitope on tau protein recognized by the monoclonal antibody Alz50 was defined through internal deletion mutagenesis and quantified by a ffinity measurements. The epitope is discontinuous and requires both a previously identified N-terminal segment and the microtubule binding region for efficient binding of Alz50. The interaction between these r egions is consistent with an intramolecular reaction mechanism, sugges ting that Alz50 binding depends on the conformation of individual tau monomers. The results suggest that tau adopts a distinct conformation when polymerized into filaments and that this conformation is recogniz ed selectively by Alz50.