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Updated: Mar 18, 2026
Detection of Abnormal Prion Protein by Immunohistochemistry
Published on: May 5, 2023
The Anti-Prion Antibody 15B3 Detects Toxic Amyloid-β Oligomers
Matteo Stravalaci1, Laura Tapella2, Marten Beeg1
1Department of Molecular Biochemistry and Pharmacology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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.
Insights
The 15B3 antibody, initially targeting prion protein aggregates, unexpectedly binds to amyloid-beta (Aβ)42 oligomers. This discovery offers a potential new tool for Alzheimer's disease (AD) research, diagnostics, and therapeutics.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Prion protein (PrP) aggregation is linked to neurodegenerative diseases.
- Amyloid-beta (Aβ)42 oligomers are implicated in Alzheimer's disease (AD) pathogenesis.
- Monoclonal antibodies are valuable tools for studying protein aggregation.
Purpose of the Study:
- To investigate the binding properties of the 15B3 antibody.
- To explore the potential of 15B3 as a tool for Alzheimer's disease (AD).
Main Methods:
- Characterization of 15B3 antibody binding to amyloid-beta (Aβ)42 oligomers.
- Inhibition assays using synthetic Aβ42 oligomers, recombinant PrP, and neuronal membranes.
- Functional assays in Caenorhabditis elegans and mouse models of Alzheimer's disease (AD).
Main Results:
- The 15B3 antibody recognizes oligomeric but not monomeric forms of Aβ42.
- 15B3 inhibits Aβ42 oligomer binding to PrP and neuronal membranes.
- 15B3 prevents Aβ42 oligomer-induced membrane depolarization and antagonizes oligomer effects in C. elegans.
- 15B3 counteracts Aβ42 oligomer-induced memory deficits in mice.
Conclusions:
- The 15B3 antibody binds to pathologically relevant Aβ42 oligomers.
- 15B3 demonstrates potential as a research, diagnostic, and therapeutic tool for Alzheimer's disease (AD).
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