{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:55:10Z","timestamp":1790794510977,"version":"4.1.0"},"reference-count":42,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"40","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,10,2]]},"abstract":"<jats:p>\n                    Misfolded alpha-Synuclein (\u03b1-Syn) accumulation is the defining molecular pathology of Parkinson\u2019s disease (PD), yet blood-based assays remain challenged by the high background of peripheral \u03b1-Syn originating mainly from red blood cells. Neuronal extracellular vesicles (EVs) circulating in blood offer a biologically enriched source of brain-derived \u03b1-Syn proteoforms, but their ultralow abundance has hindered reliable detection. Here, we introduce an organic electrochemical transistor\u2013based multiparametric diagnostic assay that simultaneously detects total, aggregated, and serine-129\u2013phosphorylated \u03b1-Syn proteoforms in serum L1CAM\n                    <jats:sup>+<\/jats:sup>\n                    EVs. The platform achieves low femtomolar sensitivity in buffer and robust analytical performance in clinical specimens. In a cohort of 66 individuals, including prodromal and clinically diagnosed patients with PD, combining the three proteoform readouts distinguished PD from controls with 90.9% accuracy (88.6% sensitivity and 90.9% specificity). By electronically amplifying and resolving multiple neuronal \u03b1-Syn signatures in blood, this assay enables a minimally invasive diagnostic tool for early-stage PD and provides a path toward therapeutic intervention during the window when disease-modifying treatments are likely to be most effective.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aee4525","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:58:26Z","timestamp":1790791106000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Electronic profiling of neuronal extracellular vesicles enables early prediction of Parkinson\u2019s disease"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6614-1538","authenticated-orcid":true,"given":"Tianrui","family":"Chang","sequence":"first","affiliation":[{"name":"Organic Bioelectronics Laboratory, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4386-0740","authenticated-orcid":true,"given":"Cheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK."},{"name":"Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK."},{"name":"School of Medicine, Life and Health Sciences, Chinese University of Hong Kong, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4933-4238","authenticated-orcid":true,"given":"Shijun","family":"Yan","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK."},{"name":"Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK."},{"name":"Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3059-4503","authenticated-orcid":true,"given":"Shofarul","family":"Wustoni","sequence":"additional","affiliation":[{"name":"Organic Bioelectronics Laboratory, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7484-1120","authenticated-orcid":true,"given":"Luca","family":"Salvigni","sequence":"additional","affiliation":[{"name":"Organic Bioelectronics Laboratory, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi 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Oxford, Oxford, UK."},{"name":"Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6383-6321","authenticated-orcid":true,"given":"Keying","family":"Guo","sequence":"additional","affiliation":[{"name":"Organic Bioelectronics Laboratory, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia."},{"name":"Department of Biotechnology and Food Engineering, Guangdong Technion\u2013Israel Institute of Technology (GTIIT), Guangdong 515063, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1166-1512","authenticated-orcid":true,"given":"Sahika","family":"Inal","sequence":"additional","affiliation":[{"name":"Organic Bioelectronics Laboratory, Biological and Environmental Science and Engineering Division, King Abdullah University 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