{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T18:08:18Z","timestamp":1781806098857,"version":"3.54.5"},"reference-count":92,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T00:00:00Z","timestamp":1735948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Singapore National Medical Research Council (NMRC)"},{"name":"STaR"},{"name":"CS-IRG"},{"name":"OF-IRG"},{"name":"HLCA"},{"name":"Duke-Duke-NUS Collaboration Pilot Grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is the second most common neurodegenerative disease in the world. Currently, PD is incurable, and the diagnosis of PD mainly relies on clinical manifestations. The central pathological event in PD is the abnormal aggregation and deposition of misfolded \u03b1-synuclein (\u03b1-Syn) protein aggregates in the Lewy body (LB) in affected brain areas. Behaving as a prion-like seeding, the misfolded \u03b1-syn protein can induce and facilitate the aggregation of native unfolded \u03b1-Syn protein to aggravate \u03b1-Syn protein aggregation, leading to PD progression. Recently, in a blood-based \u03b1-Syn seeding amplification assay (SAA), Kluge et al. identified pathological \u03b1-Syn seeding activity in PD patients with Parkin (PRKN) gene variants. Additionally, pathological \u03b1-syn seeding activity was also identified in sporadic PD and PD patients with Leucine-rich repeat kinase 2 (LRRK2) or glucocerebrosidase (GBA) gene variants. Principally, the \u03b1-Syn SAA can be used to detect pathological \u03b1-Syn seeding activity, which will significantly enhance PD diagnosis, progression monitoring, prognosis prediction, and anti-PD therapy. The significance and future strategies of \u03b1-Syn SAA protocol are highlighted and proposed, whereas challenges and limitations of the assay are discussed.<\/jats:p>","DOI":"10.3390\/ijms26010389","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T08:08:52Z","timestamp":1736150932000},"page":"389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The \u03b1-Synuclein Seeding Amplification Assay for Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5250-214X","authenticated-orcid":false,"given":"Ling-Xiao","family":"Yi","sequence":"first","affiliation":[{"name":"National Neuroscience Institute of Singapore, 11 Jalan Tan Tock Seng, Singapore 30843, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eng King","family":"Tan","sequence":"additional","affiliation":[{"name":"National Neuroscience Institute of Singapore, 11 Jalan Tan Tock Seng, Singapore 30843, Singapore"},{"name":"Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore"},{"name":"Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0251-4163","authenticated-orcid":false,"given":"Zhi Dong","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Neuroscience Institute of Singapore, 11 Jalan Tan Tock Seng, Singapore 30843, Singapore"},{"name":"Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,4]]},"reference":[{"key":"ref_1","first-page":"1483","article-title":"Beyond tremor and rigidity: Non-motor features of Parkinson\u2019s disease","volume":"116","author":"Storch","year":"2009","journal-title":"J. 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