{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T13:04:46Z","timestamp":1792501486574,"version":"4.5.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"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":"DRI Ltd","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["669237"],"award-info":[{"award-number":["669237"]}],"id":[{"id":"10.13039\/100010663","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"}]},{"name":"Herchel Smith Postdoctoral Fellowship"},{"name":"RCUK\/UKRI Research Innovation Fellowship"},{"DOI":"10.13039\/501100000265","name":"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\/501100019544","name":"Cambridge Centre for Parkinson-Plus","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019544","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge Biomedical Research Centre Dementia and Neurodegeneration Theme","doi-asserted-by":"publisher","award":["146281"],"award-info":[{"award-number":["146281"]}],"id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NHS, the NIHR or the Department of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Aggregation of \u03b1-synuclein plays a key role in the development of Parkinson\u2019s disease. Soluble aggregates are present not only within human brain but also the CSF and blood. Characterizing the aggregates present in these biofluids may provide insights into disease mechanisms and also have potential for aiding diagnosis.<\/jats:p>\n               <jats:p>We used two optical single-molecule imaging methods called aptamer DNA-PAINT and single-aggregate confocal fluorescence, together with high-resolution atomic force microscopy for specific detection and characterization of individual aggregates with intermolecular \u03b2-sheet structure, present in the CSF and serum of 15 early stage Parkinson\u2019s disease patients compared to 10 healthy age-matched controls.<\/jats:p>\n               <jats:p>We found aggregates ranging in size from 20 nm to 200 nm, in both CSF and serum. There was a difference in aggregate size distribution between Parkinson\u2019s disease and control groups with a significantly increased number of larger aggregates (longer than 150 nm) in the serum of patients with Parkinson\u2019s disease. To determine the chemical composition of the aggregates, we performed aptamer DNA-PAINT on serum following \u03b1-synuclein and amyloid-\u03b2 immunodepletion in an independent cohort of 11 patients with early stage Parkinson\u2019s disease and 10 control subjects. \u03b2-Sheet aggregates in the serum of Parkinson\u2019s disease patients were found to consist of, on average, 50% \u03b1-synuclein and 50% amyloid-\u03b2 in contrast to 30% \u03b1-synuclein and 70% amyloid-\u03b2 in control serum [the differences in the proportion of these aggregates were statistically significant between diseased and control groups (P = 1.7 \u00d7 10\u22125 for each species)]. The ratio of the number of \u03b2-sheet \u03b1-synuclein aggregates to \u03b2-sheet amyloid-\u03b2 aggregates in serum extracted using our super-resolution method discriminated Parkinson\u2019s disease cases from controls with an accuracy of 98.2% (AUC = 98.2%, P = 4.3 \u00d7 10\u22125).<\/jats:p>\n               <jats:p>Our data suggest that studying the protein aggregates present in serum can provide information about the disruption of protein homeostasis occurring in Parkinson\u2019s disease and warrants further investigation as a potential biomarker of disease.<\/jats:p>","DOI":"10.1093\/brain\/awab306","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T19:15:36Z","timestamp":1629141336000},"page":"632-643","source":"Crossref","is-referenced-by-count":63,"title":["Imaging protein aggregates in the serum and cerebrospinal fluid in Parkinson\u2019s disease"],"prefix":"10.1093","volume":"145","author":[{"given":"Evgeniia","family":"Lobanova","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Whiten","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1232-1907","authenticated-orcid":false,"given":"Francesco S","family":"Ruggeri","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK"},{"name":"Laboratory of Organic Chemistry, Wageningen University, Stippeneng 4, Wageningen 6703 WE, The Netherlands"},{"name":"Laboratory of Physical Chemistry, Wageningen University, Stippeneng 4, Wageningen 6703 WE, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8449-8704","authenticated-orcid":false,"given":"Christopher G","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6553-6154","authenticated-orcid":false,"given":"Antonina","family":"Kouli","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0PY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5977-9691","authenticated-orcid":false,"given":"Zengjie","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derya","family":"Emin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK"},{"name":"UK Dementia Research Institute at Cambridge, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu P","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff Y L","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, 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, 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