Alzheimer's disease is a progressive neurodegenerative disorder characterized by neurofibrillary tangles and depositionof plaques containing the amyloid-ß (Aß) peptide. Aß is derived through proteolytic cleavage of the amyloid precursor protein resulting in various peptide lengths corresponding to 38-43 amino acids. Aß1-42 is particularly prone to self-aggregate and its aggregates are strongly linked to development of the disease. During in vitro Aß self-assembly, highly cytotoxic metastable intermediates (oligomers) are generated ranging from 8 kDa to over 100 kDa. Several reports suggest a similar situation in vivo. We have generated a monoclonal antibody, specific for Aß oligomers, by immunizing mice with partly aggregated Aß1-40 peptide. The antibody 4D8 is a conformational specific antibody that specifically can detect oligomeric structures of Aß (1-42). The reactivity is strongly enhanced within an oligomeric range of approximately 4-15 Aß monomers while it shows only very low affinity towards mature fibrils and soluble monomers.