{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:51:46Z","timestamp":1775818306079,"version":"3.50.1"},"posted":{"date-parts":[[2023,12,23]]},"group-title":"Neuroscience","reference-count":6,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Exosomes are proposed to be important in the pathogenesis of prevalent neurodegenerative diseases. We report the first application of solid-state technology to perform multiplex analysis of single exosomes in human cerebrospinal fluid (CSF) obtained from the lumbar sac of people diagnosed with Alzheimer\u2019s disease dementia (ADD, n=30) or Parkinson\u2019s disease dementia (PDD, n=30), as well as age-matched health controls (HCN, n=30). Single events were captured with mouse monoclonal antibodies to one of three different tetraspanins (CD9, CD63, or CD81) or with mouse (M) IgG control, and then probed with fluorescently labeled antibodies to prion protein (PrP) or CD47 to mark neuronal or presynaptic origin, as well as ADD- and PDD-related proteins: amyloid beta (A\u03b2), tau, \u03b1-synuclein, and Apolipoprotein (Apo) E. Data were collected only from captured events that were within the size range of 50 to 200 nm. Exosomes were present at approximately 100 billion per mL human CSF and were similarly abundant for CD9+ and CD81+ events, but CD63+ were only 22% to 25% of CD9+ (P&lt;0.0001) or CD81+ (P&lt;0.0001) events. Approximately 24% of CSF exosomes were PrP+, while only 2% were CD47+. The vast majority of exosomes were surface ApoE+, and the number of PrP-ApoE+ (P&lt;0.001) and PrP+ApoE+ (P&lt;0.01) exosomes were significantly reduced in ADD vs. HCN for CD9+ events only. A\u03b2, tau, and \u03b1-synuclein were not detected on the exosome surface or in permeabilized cargo. These data provide new insights into single exosome molecular features and highlight reduction in the CSF concentration of ApoE+ exosomes in patients with ADD.<\/jats:p>","DOI":"10.1101\/2023.12.22.573124","type":"posted-content","created":{"date-parts":[[2023,12,23]],"date-time":"2023-12-23T21:05:24Z","timestamp":1703365524000},"source":"Crossref","is-referenced-by-count":3,"title":["Human cerebrospinal fluid single exosomes in Parkinson\u2019s and Alzheimer\u2019s diseases"],"prefix":"10.64898","author":[{"given":"Koya","family":"Yakabi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eloise","family":"Berson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen S.","family":"Montine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1341-2453","authenticated-orcid":false,"given":"Sean C.","family":"Bendall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1853-0256","authenticated-orcid":false,"given":"Michael J.","family":"MacCoss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen L.","family":"Poston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Montine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023122708300556000_2023.12.22.573124v1.1","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1007\/s00216-022-04174-5","article-title":"A review on comparative studies addressing exosome isolation methods from body fluids","volume":"415","year":"2023","journal-title":"Anal Bioanal Chem"},{"key":"2023122708300556000_2023.12.22.573124v1.2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/jnc.15697","article-title":"Extracellular vesicles in the study of Alzheimer\u2019s and Parkinson\u2019s diseases: Methodologies applied from cells to biofluids","volume":"163","year":"2022","journal-title":"J Neurochem"},{"key":"2023122708300556000_2023.12.22.573124v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"2023122708300556000_2023.12.22.573124v1.4","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1002\/ana.26574","article-title":"Illusory Responses across the Lewy Body Disease Spectrum","volume":"93","year":"2023","journal-title":"Ann Neurol"},{"key":"2023122708300556000_2023.12.22.573124v1.5","doi-asserted-by":"crossref","unstructured":"Nolan JP and Duggan E. Analysis of Individual Extracellular Vesicles by Flow Cytometry. In: Flow Cytometry Protocols, Methods in Molecular Biology, TS Hawley and RG Hawley, eds. 2018, Springer: Berlin. p. 79\u201392.","DOI":"10.1007\/978-1-4939-7346-0_5"},{"key":"2023122708300556000_2023.12.22.573124v1.6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1521230113"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.12.22.573124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:42:33Z","timestamp":1768455753000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.12.22.573124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,23]]},"references-count":6,"URL":"https:\/\/doi.org\/10.1101\/2023.12.22.573124","relation":{},"subject":[],"published":{"date-parts":[[2023,12,23]]},"subtype":"preprint"}}