The Anti-Prion Antibody 15B3 Detects Toxic Amyloid-β Oligomers

B3 is a monoclonal IgM antibody that selectively detects pathological aggregates of the prion protein (PrP). We report the unexpected finding that 15B3 also recognizes oligomeric but not monomeric forms of amyloid- (A)42 ,a n aggregating peptide implicated in the pathogenesis of Alzheimer's disease (AD). The 15B3 antibody: i) inhibits the bind- ing of synthetic A42 oligomers to recombinant PrP and neuronal membranes; ii) prevents oligomer-induced membrane depolarization; iii) antagonizes the inhibitory effects of oligomers on the physiological pharyngeal contractions of the nema- tode Caenorhabditis elegans; and iv) counteracts the memory deficits induced by intracerebroventricular injection of A42 oligomers in mice. Thus this antibody binds to pathologically relevant forms of A, and offers a potential research, diagnostic, and therapeutic tool for AD.