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Fox Foundation for Parkinson\u2019s Research"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG067607"],"award-info":[{"award-number":["AG067607"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The BAND grant jointly funded by the Alzheimer\u2019s Association, Alzheimer\u2019s Research UK, Michael J. Fox Foundation for Parkinson\u2019s Research, and Weston Brain Institute and the CJD Foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Synucleinopathies, including Parkinson\u2019s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), share pathological accumulation of misfolded \u03b1-synuclein (\u03b1Syn) in the brain and overlapping clinical features, complicating accurate diagnosis with current methods. In this study, we utilized a real-time quaking-induced conversion (RT-QuIC) assay to demonstrate that autopsied skin samples from PD, DLB, and MSA patients (but not non-synucleinopathy controls) seed aggregation of recombinant \u03b1Syn. While RT-QuIC generated similarly positive fluorescence kinetic curves across synucleinopathies, biochemical and morphological analyses of RT-QuIC end products revealed distinct properties in the resulting \u03b1Syn aggregates. Notably, \u03b1Syn aggregates from DLB samples exhibited the highest resistance to proteinase K digestion, whereas MSA-derived aggregates showed the least aggregated bands on Western blots. Transmission electron microscopy revealed significant differences in length, width, and volume of skin \u03b1Syn fibrils of RT-QuIC end products from different synucleinopathies. These findings provide critical insights into disease-specific \u03b1Syn structural characteristics and suggest new strategies to improve diagnostic discrimination.<\/jats:p>","DOI":"10.1007\/s00401-025-02973-5","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T07:49:59Z","timestamp":1768204199000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Biochemical signatures of skin \u03b1-synuclein in synucleinopathies revealed by RT-QuIC assay end-product analysis"],"prefix":"10.1007","volume":"151","author":[{"given":"Maria","family":"Gerasimenko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hancun","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tricia","family":"Gilliland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zerui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Quan","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"key":"2973_CR1","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/jnc.14808","volume":"150","author":"P Alam","year":"2019","unstructured":"Alam P, Bousset L, Melki R, Otzen DE (2019) \u03b1-synuclein oligomers and fibrils: a spectrum of species, a spectrum of toxicities. 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