Antibodies to cross-linked amyloid beta oligomers

Abstract

The invention relates to antibodies that bind cross-linked amyloid β oligomers, and methods for using such antibodies for diagnosis and treatment of Alzheimer's disease.

1 . A method for diagnosing Alzheimer's disease in a subject comprising
 obtaining a biological sample from a subject,   determining the presence of antibodies reactive with oxidized forms of amyloid β in the blood or plasma sample, wherein the lack of antibodies reactive with oxidized forms of amyloid β, or a reduced level of antibodies reactive with oxidized forms of amyloid β relative to a control indicates that the subject has Alzheimer's disease.   
     
     
         2 . The method of  claim 1 , wherein the biological sample is a blood sample or plasma sample. 
     
     
         3 . The method of  claim 1 , wherein the oxidized forms of amyloid β used to determine the presence of antibodies are cross-linked β-amyloid protein species (CLAPS). 
     
     
         4 . The method of  claim 3 , wherein the CLAPS are 15-35 kDa. 
     
     
         5 . The method of  claim 3 , wherein the CLAPS are formed by oxidation of amyloid β with horse radish peroxidase in the presence of hydrogen peroxide. 
     
     
         6 . The method of  claim 1 , wherein the method used to determine the presence of antibodies reactive with oxidized forms of amyloid β is an ELISA assay. 
     
     
         7 . The method of  claim 1 , wherein the ELISA assay is a sandwich ELISA assay. 
     
     
         8 . The method of  claim 1 , wherein the control is blood or plasma from a non-demented individual. 
     
     
         9 . A method for inducing an immune response to an oxidized form of amyloid β, comprising
 administering to a subject an amount of an oxidized form of amyloid β effective to induce a specific immune response to the oxidized form of amyloid β. 
 
     
     
         10 . The method of  claim 9 , wherein the immune response is the production of antibodies that bind to the oxidized form of amyloid β. 
     
     
         11 . The method of  claim 9 , wherein the oxidized form of amyloid β is cross-linked β-amyloid protein species (CLAPS). 
     
     
         12 . The method of  claim 11 , wherein the CLAPS are 15-35 kDa. 
     
     
         13 . The method of  claim 11 , wherein the CLAPS are formed by oxidation of amyloid β with horse radish peroxidase in the presence of hydrogen peroxide. 
     
     
         14 . A method for treating or preventing Alzheimer's disease, comprising
 administering to a subject in need of such treatment an amount of antibodies, or antigen-binding fragments thereof, that bind to an oxidized form of amyloid β.   
     
     
         15 . The method of  claim 14 , wherein the oxidized form of amyloid β is cross-linked β-amyloid protein species (CLAPS). 
     
     
         16 . The method of  claim 14 , wherein the antibodies are made by administering an oxidized form of amyloid β to a mammal to produce antibodies that bind the oxidized form of amyloid β. 
     
     
         17 . The method of  claim 16 , wherein the oxidized form of amyloid β is cross-linked β-amyloidprotein species (CLAPS). 
     
     
         18 . The method of  claim 17 , wherein the CLAPS are 15-35 kDa. 
     
     
         19 . The method of  claim 16 , wherein the mammal is a non-human species comprising human immunoglobulin genes. 
     
     
         20 . The method of  claim 19 , wherein the non-human species is a mouse. 
     
     
         21 . The method of  claim 14 , wherein the antibodies or fragments thereof are human antibodies or fragments thereof. 
     
     
         22 . The method of  claim 14 , wherein the antibodies or fragments thereof are humanized or chimeric antibodies, or fragments thereof. 
     
     
         23 . The method of  claim 14 , wherein the antibody fragments are selected from the group consisting of Fab fragments, F(ab′) 2  fragments, and Fv fragments. 
     
     
         24 . The method of  claim 14 , wherein the antibodies are single chain antibodies.