{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:24:08Z","timestamp":1794007448005,"version":"4.8.0"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Detection of \u03b1\u2010synuclein aggregates by seed amplification is a promising Parkinson disease biomarker assay. Understanding intraindividual relationships of \u03b1\u2010synuclein measures could inform optimal biomarker development. The objectives were to test accuracy of \u03b1\u2010synuclein seed amplification assay in central (cerebrospinal fluid) and peripheral (submandibular gland) sources, compare to total \u03b1\u2010synuclein measures, and investigate within\u2010subject relationships.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The Systemic Synuclein Sampling Study aimed to characterize \u03b1\u2010synuclein in multiple tissues and biofluids within Parkinson disease subjects (<jats:italic>n<\/jats:italic>\u00a0=\u00a059) and compared to healthy controls (<jats:italic>n<\/jats:italic>\u00a0=\u00a021). Motor and non\u2010motor measures and dopamine transporter scans were obtained. Four measures of \u03b1\u2010synuclein were compared: seed amplification assay in cerebrospinal fluid and formalin\u2010fixed paraffin\u2010embedded submandibular gland, total \u03b1\u2010synuclein quantified in biofluids using enzyme\u2010linked immunoassay, and aggregated \u03b1\u2010synuclein in submandibular gland detected by immunohistochemistry. Accuracy of seed amplification assay for Parkinson disease diagnosis was examined and within\u2010subject \u03b1\u2010synuclein measures were compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sensitivity and specificity of \u03b1\u2010synuclein seed amplification assay for Parkinson disease diagnosis was 92.6% and 90.5% in cerebrospinal fluid, and 73.2% and 78.6% in submandibular gland, respectively. 25\/38 (65.8%) Parkinson disease participants were positive for both cerebrospinal fluid and submandibular gland seed amplification assay. Comparing accuracy for Parkinson disease diagnosis of different \u03b1\u2010synuclein measures, cerebrospinal fluid seed amplification assay was the highest (Youden Index\u00a0=\u00a083.1%). 98.3% of all Parkinson disease cases had \u22651 measure of \u03b1\u2010synuclein positive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>\u03b1\u2010synuclein seed amplification assay (cerebrospinal fluid&gt;submandibular gland) had higher sensitivity and specificity compared to total \u03b1\u2010synuclein measures, and within\u2010subject relationships of central and peripheral \u03b1\u2010synuclein measures emerged.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51753","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:09:41Z","timestamp":1679962181000},"page":"696-705","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Central and peripheral \u03b1\u2010synuclein in Parkinson disease detected by seed amplification assay"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2521-7196","authenticated-orcid":false,"given":"Lana M.","family":"Chahine","sequence":"first","affiliation":[{"name":"Department of Neurology University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"Beach","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute Sun City Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles H.","family":"Adler","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic College of Medicine Scottsdale Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Hepker","sequence":"additional","affiliation":[{"name":"Biomedical Sciences Iowa State University Ames Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6454-4264","authenticated-orcid":false,"given":"Anumantha","family":"Kanthasamy","sequence":"additional","affiliation":[{"name":"Center for Brain Science and Neurodegenerative Diseases, Department of Physiology and Pharmacology University of Georgia Athens Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Appel","sequence":"additional","affiliation":[{"name":"Biostatistics Analysis Center University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Pritzkow","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Texas, McGovern Medical School Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Pinho","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Texas, McGovern Medical School Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherri","family":"Mosovsky","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geidy E.","family":"Serrano","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute Sun City Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Coffey","sequence":"additional","affiliation":[{"name":"Banner Sun Health Research Institute Sun City Arizona USA"},{"name":"Department of Biostatistics University of Iowa College of Public Health Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Brumm","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Iowa College of Public Health Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis M. 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