The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aß-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimers Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimers Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLs, and tauphosphorylation and are therefore useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid ß 1-42.