{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:23:17Z","timestamp":1790083397487,"version":"4.0.1"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research (MUR)","award":["PE0000006"],"award-info":[{"award-number":["PE0000006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Clinical differentiation between Parkinson\u2019s disease (PD) and essential tremor (ET) may be challenging, highlighting the need for easily assessable diagnostic biomarkers. Neuronally derived extracellular vesicles (NDEVs) have been proposed as a peripheral matrix that can well recapitulate the cellular composition of neurons. We investigated the clinical usefulness of NDEV oligomeric and p129-\u03b1-synuclein levels in discriminating between patients with PD and those with ET. NDEV oligomeric and p129-\u03b1-synuclein species were assessed using an ELISA in 43 patients with PD, 21 patients with ET, and 45 healthy controls (HCs). NDEV oligomeric \u03b1-synuclein levels were significantly higher in PD in comparison with ET and HCs, while p129-\u03b1-synuclein values were significantly lower in HCs compared to other groups. By using a receiver operator characteristic (ROC) analysis, oligomeric-\u03b1-synuclein achieved an excellent classification performance in distinguishing PD from both ET and HCs (AUC: 0.976 and 0.997, respectively), while lower performance was obtained in differentiating ET from HCs (AUC: 0.85). On the other hand, p129-\u03b1-synuclein accurately discriminated both PD and ET from HCs (AUC: 0.997 and 0.952, respectively) but had very low performance in differentiating PD from ET (AUC: 0.47). Our study suggests that NDEV oligomeric \u03b1-synuclein is an accurate blood-derived biomarker to differentiate PD from ET, while p129-\u03b1-synuclein may be useful in distinguishing ET from HCs.<\/jats:p>","DOI":"10.3390\/ijms26083819","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T20:50:46Z","timestamp":1744923046000},"page":"3819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Neuronally Derived Extracellular Vesicles\u2019 Oligomeric and p129-\u03b1-Synuclein Levels for Differentiation of Parkinson\u2019s Disease from Essential Tremor"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7811-2083","authenticated-orcid":false,"given":"Costanza Maria","family":"Cristiani","sequence":"first","affiliation":[{"name":"Neuroscience Research Center, Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2187-9176","authenticated-orcid":false,"given":"Selena","family":"Mimmi","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8145-3623","authenticated-orcid":false,"given":"Elvira Immacolata","family":"Parrotta","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells, Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariagrazia","family":"Talarico","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells, Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5077-0845","authenticated-orcid":false,"given":"Anna Maria","family":"Tolomeo","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Research Citt\u00e0 della Speranza, 35128 Padua, Italy"},{"name":"Department of Cardiac, Thoracic and Vascular Science and Public Health, University of Padova, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Pingitore","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khushboo","family":"Fatima","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7172-8520","authenticated-orcid":false,"given":"Basilio","family":"Vescio","sequence":"additional","affiliation":[{"name":"Biotecnomed S.c.ar.l., 88100 Catanzaro, Italy"},{"name":"IBSBC-CNR, Via T. Campanella, 115, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3239-3745","authenticated-orcid":false,"given":"Luana","family":"Scaramuzzino","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Crapella","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8334-0005","authenticated-orcid":false,"given":"Anna Maria","family":"Zimbo","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3565-7817","authenticated-orcid":false,"given":"Enrico","family":"Iaccino","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6313-1866","authenticated-orcid":false,"given":"Giovanni","family":"Cuda","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Quattrone","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2071-2083","authenticated-orcid":false,"given":"Andrea","family":"Quattrone","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"},{"name":"Institute of Neurology, Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S162","DOI":"10.1016\/j.parkreldis.2015.09.032","article-title":"The relationship between essential tremor and Parkinson\u2019s disease","volume":"22","author":"Thenganatt","year":"2016","journal-title":"Parkinsonism Relat. 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