{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T13:04:44Z","timestamp":1792501484385,"version":"4.5.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":141,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000304","name":"Parkinson\u2019s UK","doi-asserted-by":"publisher","award":["G-1901"],"award-info":[{"award-number":["G-1901"]}],"id":[{"id":"10.13039\/501100000304","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK Dementia Research Institute Ltd"},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R007446\/1"],"award-info":[{"award-number":["MR\/R007446\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017506","name":"Alzheimer\u2019s Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017506","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W029235\/1"],"award-info":[{"award-number":["MR\/W029235\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute for Health"},{"name":"Care Research Cambridge Biomedical Research Centre","award":["NIHR203312"],"award-info":[{"award-number":["NIHR203312"]}]},{"name":"National Health Service"},{"name":"Care Research"},{"DOI":"10.13039\/501100003921","name":"Department of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Saliva is a convenient and accessible biofluid that has potential as a future diagnostic tool for Parkinson\u2019s disease. Candidate diagnostic tests for Parkinson\u2019s disease to date have predominantly focused on measurements of \u03b1-synuclein in CSF, but there is a need for accurate tests utilizing more easily accessible sample types. Prior studies utilizing saliva have used bulk measurements of salivary \u03b1-synuclein to provide diagnostic insight. Aggregate structure may influence the contribution of \u03b1-synuclein to disease pathology. Single-molecule approaches can characterize the structure of individual aggregates present in the biofluid and may, therefore, provide greater insight than bulk measurements. We have employed an antibody-based single-molecule pulldown assay to quantify salivary \u03b1-synuclein and amyloid-\u03b2 peptide aggregate numbers and subsequently super-resolved captured aggregates using direct Stochastic Optical Reconstruction Microscopy to describe their morphological features. We show that the salivary \u03b1-synuclein aggregate\/amyloid-\u03b2 aggregate ratio is increased almost 2-fold in patients with Parkinson\u2019s disease (n = 20) compared with controls (n = 20, P &amp;lt; 0.05). Morphological information also provides insight, with saliva from patients with Parkinson\u2019s disease containing a greater proportion of larger and more fibrillar amyloid-\u03b2 aggregates than control saliva (P &amp;lt; 0.05). Furthermore, the combination of count and morphology data provides greater diagnostic value than either measure alone, distinguishing between patients with Parkinson\u2019s disease (n = 17) and controls (n = 18) with a high degree of accuracy (area under the curve = 0.87, P &amp;lt; 0.001) and a larger dynamic range. We, therefore, demonstrate for the first time the application of highly sensitive single-molecule imaging techniques to saliva. In addition, we show that aggregates present within saliva retain relevant structural information, further expanding the potential utility of saliva-based diagnostic methods.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae178","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T13:58:17Z","timestamp":1716299897000},"source":"Crossref","is-referenced-by-count":5,"title":["Single-molecule characterization of salivary protein aggregates from Parkinson\u2019s disease patients: a pilot study"],"prefix":"10.1093","volume":"6","author":[{"given":"Martin","family":"Furlepa","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Cambridge , Cambridge CB2 1EW , UK"},{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge CB2 0PY , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu P","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cambridge , Cambridge CB2 1EW , UK"},{"name":"UK Dementia Research Institute at Cambridge , Cambridge CB2 0XY , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7605-5820","authenticated-orcid":false,"given":"Evgeniia","family":"Lobanova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cambridge , Cambridge CB2 1EW , UK"},{"name":"UK Dementia Research Institute at Cambridge , Cambridge CB2 0XY , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakmini","family":"Kahanawita","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge CB2 0PY , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Vivacqua","sequence":"additional","affiliation":[{"name":"Microscopic and Ultrastructural Anatomy Research Unit-Integrated Research Centre (PRABB), Campus Biomedico University of Rome , 00128 Rome , Italy"},{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge CB2 0AH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline H","family":"Williams-Gray","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge , Cambridge CB2 0PY , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cambridge , Cambridge CB2 1EW , UK"},{"name":"UK Dementia Research Institute at Cambridge , Cambridge CB2 0XY , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"issue":"8","key":"2024062808004479200_fcae178-B1","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00702-017-1686-y","article-title":"Epidemiology of Parkinson\u2019s 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