AMYLOID BETA-DERIVED DIFFUSIBLE LIGANDS (ADDLs), ADDL-BINDING MOLECULES, AND USES THEREOF
The invention herein comprises amyloid beta-derived diffusible ligands (ADDLs), compositions comprising ADDLs, ADDL-surrogates, ADDL-binding molecules, and methods of using any of the foregoing compounds and compositions. ADDLs comprise amyloid β protein assembled into soluble, globular, non-fibrillar, oligomeric structures capable of activating specific cellular processes. The invention also comprises methods of generating ADDL-specific antibodies and methods of using ADDL-specific antibodies for assaying the formation, presence, receptor protein binding and cellular activity of ADDLs, as well as using such antibodies to detect compounds that block the formation or activity of ADDLs, and methods of identifying such compounds. The invention further provides methods of using ADDL-specific antibodies in modulating ADDL formation and/or activity, inter alia in the treatment of learning and/or memory disorders.
1 . A method for quantitatively detecting soluble oligomeric amyloid β in a biological sample comprising
(a) contacting serum, cerebrospinal fluid or post-mortem brain tissue sections with an antibody or fragment thereof exhibiting selective cross-reactivity with soluble oligomeric amyloid β over monomer and fibrillar amyloid; and
(b) quantitatively measuring binding of the antibody or fragment thereof to the serum, cerebrospinal fluid or post-mortem brain tissue sections thereby quantitatively detecting soluble oligomeric amyloid β in a biological sample.
2 . The method of claim 1 , wherein the antibody is a monoclonal antibody or fragment thereof.
3 . The method of claim 1 , wherein the antibody is a humanized monoclonal antibody or fragment thereof.