Specific recognition of biologically active amyloid-β oligomers by a new surface plasmon resonance-based immunoassay and an in vivo assay in Caenorhabditis elegans

Matteo Stravalaci, Antonio Bastone, Marten Beeg, Alfredo Cagnotto, Laura Colombo, Giuseppe Di Fede, Fabrizio Tagliavini, Laura Cantù, Elena Del Favero, Michele Mazzanti, Roberto Chiesa, Mario Salmona, Luisa Diomede, Marco Gobbi

Research output: Contribution to journalArticle


Soluble oligomers of the amyloid-β (Aβ) peptide play a key role in the pathogenesis of Alzheimer's disease, but their elusive nature makes their detection challenging. Here we describe a novel immunoassay based on surface plasmon resonance (SPR) that specifically recognizes biologically active Aβ oligomers. As a capturing agent, we immobilized on the sensor chip the monoclonal antibody 4G8, which targets a central hydrophobic region of Aβ. This SPR assay allows specific recognition of oligomeric intermediates that rapidly appear and disappear during the incubation of synthetic Aβ1-42, discriminating them from monomers and higher order aggregates. The species recognized by SPR generate ionic currents in artificial lipid bilayers and inhibit the physiological pharyngeal contractions in Caenorhabditis elegans, a new method for testing the toxic potential of Aβ oligomers. With these assays we found that the formation of biologically relevant Aβ oligomers is inhibited by epigallocatechin gallate and increased by the A2V mutation, previously reported to induce early onset dementia. The SPR-based immunoassay provides new opportunities for detection of toxic Aβ oligomers in biological samples and could be adapted to study misfolding proteins in other neurodegenerative disorders.

Original languageEnglish
Pages (from-to)27796-27805
Number of pages10
JournalJournal of Biological Chemistry
Issue number33
Publication statusPublished - Aug 10 2012


ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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