Alpha-Synuclein Conformations in Plasma Distinguish Parkinson’s Disease from Dementia with Lewy Bodies

Alpha-Synuclein Conformations in Plasma Distinguish Parkinson’s Disease from Dementia with Lewy Bodies | 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 Alpha-Synuclein Conformations in Plasma Distinguish Parkinson’s Disease from Dementia with Lewy Bodies Alice Chen-Plotkin, George Kannarkat, Rebecca Zack, R. Tyler Skrinak, and 14 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5033901/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aggregation of misfolded alpha-synuclein (aSyn) within the brain is the pathologic hallmark of Lewy body diseases (LBD), including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Evidence exists for aSyn “strains” – conformations with distinct biological properties. However, biomarkers for PD vs. DLB, including potential aSyn strain differences, are lacking. Here, we used two monoclonal antibodies selective for different in vitro aSyn species – termed Strain A and B – to evaluate human brain tissue, cerebrospinal fluid (CSF), and plasma. Surprisingly, levels of Strain A and B aSyn species differed in plasma from individuals with PD vs. DLB in two independent cohorts. Lower plasma aSyn Strain A species also predicted subsequent PD cognitive decline. Strain A and Strain B aSyn species were undetectable in CSF, but plasma aSyn species could template aSyn fibrillization, particularly in PD. Our findings suggest that aSyn strains may impact LBD clinical presentation and originate outside the brain. Health sciences/Neurology/Neurological disorders/Parkinson's disease Health sciences/Neurology/Neurological disorders/Neurodegenerative diseases Full Text Additional Declarations There is NO Competing Interest. Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-5033901","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":354088911,"identity":"63a5c637-5f4b-4b02-8e9d-b5e8c0e4fd6d","order_by":0,"name":"Alice Chen-Plotkin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFklEQVRIiWNgGAWjYDACdsYGIHkAiJmBjAMSDPwg0YQCPFqY4VqAjANALZIgfoIBPi1gEq6FgcEAxGbAo4W/mbnxw4eaO3Lm0o2Njz+cscgzPr868cMDAwZ5frEDWLVIHGZslpxx7Jmx5ZyDzQYHbkgUm914u1kC6DDDmbMTsFtzmLGNmbfhcOKGG4ltEgc+SCRuu3F2A0hLgsFt7FrkQVr+Nhyuh2vZPOPs5h/4tBiAtDA2HE4wAGu5IZG4gb93G15bDEF+6Tl22HDDHaBfzpyRSJxxg3ebRYKBBE6/yB1vf/jhR81heYPbzQcfVByrS+zvP7v55o8KG3l+aRzehwMJOCMBhUuMFv4DRKgeBaNgFIyCkQQAZANvR2T7IJoAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-3387-2038","institution":"University of Pennsylvania","correspondingAuthor":true,"prefix":"","firstName":"Alice","middleName":"","lastName":"Chen-Plotkin","suffix":""},{"id":354088912,"identity":"a05e63d9-b28e-4503-a09e-b5489a2c0119","order_by":1,"name":"George Kannarkat","email":"","orcid":"","institution":"University of Pennsylvania","correspondingAuthor":false,"prefix":"","firstName":"George","middleName":"","lastName":"Kannarkat","suffix":""},{"id":354088913,"identity":"d6901418-03d4-477e-af6d-60595122ed31","order_by":2,"name":"Rebecca Zack","email":"","orcid":"","institution":"University of Pennsylvania","correspondingAuthor":false,"prefix":"","firstName":"Rebecca","middleName":"","lastName":"Zack","suffix":""},{"id":354088914,"identity":"df2ef8d0-353a-434c-863d-5649dd93cdb7","order_by":3,"name":"R. 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