Antibodies specific for soluble amyloid beta peptide protofibrils and uses thereof

Abstract

The invention relates to an isolated monoclonal antibody or antigen-binding fragment thereof that (a) binds (i) wild-type Aβ 42/40 protofibril comprising N-terminal truncated Aβ forms and (ii) Aβ 42/40 Arc protofibril comprising N-terminal truncated Aβ forms and (b) has no or little cross-reactivity to Aβ 42/40 monomers. The invention further relates to a method of using such an antibody to treat Alzheimer's disease.

1 . An antibody specific for soluble amyloid beta peptide (Aβ) protofibrils and/or biologically active fragments thereof. 
     
     
         2 - 36 . (canceled) 
     
     
         37 . A method for lowering Aβ protofibril levels in the brain of a subject comprising administration to the subject an antibody or antigen-binding fragment thereof that binds Aβ40/42 arc protofibril and Aβ40/42 wild-type protofibril and has no or little cross-reactivity to Aβ40/42 monomers. 
     
     
         38 . The method of  claim 37 , wherein the antibody or antigen-binding fragment thereof, is monoclonal. 
     
     
         39 . The method of  claim 37 , wherein said antibody is an antigen-binding fragment. 
     
     
         40 . The method of  claim 37 , wherein said antibody is humanized. 
     
     
         41 . The method of  claim 37 , wherein said antibody is produced by immunizing and screening with at least>95% pure Aβ40/42 arc protofibril. 
     
     
         42 . The method of  claim 37 , wherein said antibody is produced by immunizing and screening with at least>95% pure Aβ40/42 protofibril. 
     
     
         43 . The method of  claim 37 , wherein said antibody is a protofibril conformation specific antibody or antibody fragment.