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Among the species formed during this process, soluble oligomeric intermediates are the most closely linked to neurotoxicity and are therefore an attractive target for both therapeutic and diagnostic strategies. Their conformational heterogeneity and transient nature, however, have so far hindered the development of reagents that recognize them selectively, and no fully quantitative biomarker of A\u03b242 oligomers is widely available. To address this problem, we use a rationally designed conformation\u2010specific single\u2010domain antibody, DesAbO, which binds selectively to A\u03b242 oligomers. By using enzyme\u2010linked immunosorbent assay, we show that encoding self\u2010assembling multimerization domains in the DesAbO plasmid yields multimeric variants with increased avidity toward A\u03b242 oligomers. In aggregation assays, the multimeric variants inhibited A\u03b242 aggregation at concentrations at which the monomeric form was no longer effective, with the SB175 trimer performing best. These results show how multimerization can be used to enhance the recognition of A\u03b242 oligomers and offer a route toward diagnostic and therapeutic agents for Alzheimer's disease and other protein misfolding disorders.<\/jats:p>","DOI":"10.1002\/pro.70754","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T12:39:37Z","timestamp":1787143177000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multimerization of a rationally designed nanobody for enhanced avidity toward A\u03b242 oligomers"],"prefix":"10.1002","volume":"35","author":[{"given":"Magdalena","family":"Nowinska","sequence":"first","affiliation":[{"name":"Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge 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