title: The Anti-Prion Antibody 15B3 Detects Toxic Amyloid-β Oligomers.
abstract: 15B3 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-β (Aβ)42, an aggregating peptide implicated in the pathogenesis of Alzheimer's disease (AD). The 15B3 antibody: i) inhibits the binding of synthetic Aβ42 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 nematode Caenorhabditis elegans; and iv) counteracts the memory deficits induced by intracerebroventricular injection of Aβ42 oligomers in mice. Thus this antibody binds to pathologically relevant forms of Aβ, and offers a potential research, diagnostic, and therapeutic tool for AD.
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Stravalaci
authors.affiliation: Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Tapella
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Marten
authors.initials: M
authors.lastname: Beeg
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Humanitas Clinical and Research Center, Rozzano (MI), Italy.
authors.forename: Pooja
authors.initials: P
authors.lastname: Joshi
authors.affiliation: Department of Life Science, University of Milan, Milan, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Pizzi
authors.affiliation: Department of Life Science, University of Milan, Milan, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Mazzanti
authors.affiliation: Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Balducci
authors.affiliation: Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.affiliation: Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Biasini
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Diomede
authors.affiliation: Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Chiesa
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D017173:Caenorhabditis elegans; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000628:therapy*; D010446:Peptide Fragments / Q000633:toxicity*; D011328:Prions / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies; D010446:Peptide Fragments; D011328:Prions; C075222:amyloid beta-protein (1-42)
keywords: 15B3 antibody; Alzheimer’s disease; amyloid beta-protein (1– 42); oligomers; prion protein; prions