Prion Protein as a Receptor for Amyloid-Beta Oligomers

Abstract

The invention provides methods of inhibiting suppression of long term potentiation, improving acute memory retention and spatial memory performance and treating Alzheimer's disease by administration of a PrP c antagonist or combinations thereof. Additionally, this invention provides pharmaceutical kits comprising, and methods for making and using, such combinations, as well as methods of identifying molecules that could function as PrP c antagonists.

What is claimed is: 
     
         1 . A method comprising administering a therapeutically effective amount of a PrP c  antagonist to a subject having Alzheimer's disease (AD), wherein said PrP c  antagonist comprises an anti-PrP c  antibody, or antigen-binding fragment thereof, which specifically binds to an epitope within amino acids 95 to 110 of SEQ ID NOs:2, 4, or 6. 
     
     
         2 . The method of  claim 1 , wherein said anti-PrP c  antibody is a monoclonal antibody (mAb). 
     
     
         3 . The method of  claim 2 , wherein the mAb is selected from the group consisting of a humanized antibody, a chimeric antibody, a human antibody, and antigen-binding fragments of any of the foregoing. 
     
     
         4 . The method of  claim 2 , wherein said monoclonal antibody is 6D11. 
     
     
         5 . The method of  claim 2 , wherein said monoclonal antibody is 8G8. 
     
     
         6 . The method of  claim 2 , wherein said anti-PrP c  antibody specifically binds to the same epitope as 6D11. 
     
     
         7 . The method of  claim 2 , wherein said anti-PrP c  antibody specifically binds to the same epitope as 8G8. 
     
     
         8 . The method of  claim 1 , further comprising administering an additional therapeutic agent. 
     
     
         9 . A method comprising administering a therapeutically effective amount of a PrP c  antagonist to a subject having Alzheimer's disease (AD), wherein said PrP c  antagonist comprises an anti-PrP c  antibody, or antigen-binding fragment thereof, which specifically binds to an epitope within amino acids 32 to 121 of SEQ ID NOs:2, 4, or 6. 
     
     
         10 . The method of  claim 9 , wherein said anti-PrP c  antibody is a monoclonal antibody (mAb). 
     
     
         11 . The method of  claim 10 , wherein the mAb is selected from the group consisting of a: humanized antibody, a chimeric antibody, a human antibody, and antigen-binding fragments of any of the foregoing. 
     
     
         12 . The method of  claim 9 , further comprising administering an additional therapeutic agent.