Targeting Soluble Amyloid-Beta Oligomers With a Novel Nanobody

Targeting Soluble Amyloid-Beta Oligomers With a Novel Nanobody | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Targeting Soluble Amyloid-Beta Oligomers With a Novel Nanobody Justin R. Haynes, Clayton A. Whitmore, William J. Behof, Charlotte A. Landman, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3944211/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract The classical amyloid cascade hypothesis postulates that the aggregation of amyloid plaques and the accumulation of intracellular hyperphosphorylated Tau tangles, together, lead to profound neuronal death. However, emerging research has demonstrated that soluble amyloid-b oligomers (SAbOs) accumulate early, prior to amyloid plaque formation. SAbOs induce memory impairment and disrupt cognitive function independent of amyloid-b plaques, and even in the absence of plaque formation. This work describes the development and characterization of a novel anti-SAbO (E3) nanobody generated from an alpaca immunized with SAbO. In-vitro assays and in-vivo studies using 5XFAD mice indicate that the fluorescein (FAM)-labeled E3 nanobody recognizes both SAbOs and amyloid-b plaques. The E3 nanobody traverses across the blood-brain barrier and binds to amyloid species in the brain of 5XFAD mice. Imaging of mouse brains reveals that SAbO and amyloid-b plaques are not only different in size, shape, and morphology, but also have a distinct spatial distribution in the brain. SAbOs are associated with neurons, while amyloid plaques reside in the extracellular matrix. The results of this study demonstrate that the SAbO nanobody can serve as a diagnostic agent with potential theragnostic applications in Alzheimer’s disease. Biological sciences/Biotechnology Biological sciences/Chemical biology Biological sciences/Drug discovery Biological sciences/Neuroscience Health sciences/Biomarkers Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryInformationPhamSciRep2024.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 08 Apr, 2024 Reviews received at journal 18 Mar, 2024 Reviewers agreed at journal 18 Mar, 2024 Reviewers invited by journal 16 Mar, 2024 Editor assigned by journal 16 Mar, 2024 Editor invited by journal 13 Mar, 2024 Submission checks completed at journal 13 Mar, 2024 First submitted to journal 09 Feb, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3944211","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":279626583,"identity":"8a0fc24c-a239-4b29-bd37-049e339fe04d","order_by":0,"name":"Justin R. 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