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.
The Anti-Prion Antibody 15B3 Detects Toxic Amyloid-β Oligomers / M. Stravalaci, L. Tapella, M. Beeg, A. Rossi, P. Joshi, E. Pizzi, M. Mazzanti, C. Balducci, G. Forloni, E. Biasini, M. Salmona, L. Diomede, R. Chiesa, M. Gobbi. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - 54:4(2016 Jul 06), pp. 1485-1497. [10.3233/JAD-150882]
The Anti-Prion Antibody 15B3 Detects Toxic Amyloid-β Oligomers
L. TapellaSecondo
;P. Joshi;E. Pizzi;M. Mazzanti;
2016
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.File | Dimensione | Formato | |
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Anti prion Gobbi 2016.pdf
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