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However, emerging research has demonstrated that soluble amyloid-\u03b2 oligomers (SA\u03b2Os) accumulate early, prior to amyloid plaque formation. SA\u03b2Os induce memory impairment and disrupt cognitive function independent of amyloid-\u03b2 plaques, and even in the absence of plaque formation. This work describes the development and characterization of a novel anti-SA\u03b2O (E3) nanobody generated from an alpaca immunized with SA\u03b2O. In-vitro assays and in-vivo studies using 5XFAD mice indicate that the fluorescein (FAM)-labeled E3 nanobody recognizes both SA\u03b2Os and amyloid-\u03b2 plaques. The E3 nanobody traverses across the blood\u2013brain barrier and binds to amyloid species in the brain of 5XFAD mice. Imaging of mouse brains reveals that SA\u03b2O and amyloid-\u03b2 plaques are not only different in size, shape, and morphology, but also have a distinct spatial distribution in the brain. SA\u03b2Os are associated with neurons, while amyloid plaques reside in the extracellular matrix. The results of this study demonstrate that the SA\u03b2O nanobody can serve as a diagnostic agent with potential theragnostic applications in Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1038\/s41598-024-66970-6","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T03:28:12Z","timestamp":1720754892000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Targeting soluble amyloid-beta oligomers with a novel nanobody"],"prefix":"10.1038","volume":"14","author":[{"given":"Justin R.","family":"Haynes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton A.","family":"Whitmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Behof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte A.","family":"Landman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry H.","family":"Ong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Feld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle C.","family":"Suero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste B.","family":"Greer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Gore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Printha","family":"Wijesinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne A.","family":"Matsubara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian E.","family":"Wadzinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin W.","family":"Spiller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8408-7611","authenticated-orcid":false,"given":"Wellington","family":"Pham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,12]]},"reference":[{"key":"66970_CR1","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/978-94-007-5416-4_14","volume":"65","author":"VJ De-Paula","year":"2012","unstructured":"De-Paula, V. 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