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Auton. Res."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Multiple system atrophy is a progressive neurodegenerative disorder characterized by autonomic failure, parkinsonism, and cerebellar ataxia. Phosphorylated alpha-synuclein in skin nerves has emerged as a promising biomarker, but longitudinal studies remain limited. This study evaluated changes in cutaneous alpha-synuclein deposition over time, its association with autonomic dysfunction, and its concordance with seed amplification assay findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seventeen participants with probable multiple system atrophy were followed up for 12 months  with clinical assessments, skin biopsies from posterior cervical and distal thigh regions, standardized orthostatic vital signs, and cerebrospinal fluid biomarker collection. Phosphorylated alpha-synuclein deposition was quantified using immunofluorescence microscopy and correlated with autonomic measures and seed amplification assay results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Cutaneous alpha-synuclein deposition increased from baseline to  the12-month follow-up visit. Total deposition was associated with orthostatic systolic blood pressure drop (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.80,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0001) and with higher scores on the Orthostatic Hypotension Questionnaire and Composite Autonomic Symptom Score. Posterior cervical deposition showed stronger autonomic associations than distal thigh deposition. No associations were found with global disease severity or neurofilament light chain levels. Two participants with negative seed amplification assay results showed phosphorylated alpha-synuclein on skin biopsy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this cohort, cutaneous phosphorylated alpha-synuclein increased over time and correlated with objective orthostatic hypotension and autonomic symptom burden in early synucleinopathy. Skin biopsy may serve as a minimally invasive tool to support diagnosis, monitor progression, and stratify clinical trial participants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10286-026-01235-y","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T17:15:30Z","timestamp":1786554930000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cutaneous alpha-synuclein deposition informs autonomic function in individuals with early-stage multiple system atrophy"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9753-7071","authenticated-orcid":false,"given":"Paula","family":"Trujillo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailey","family":"Bellaire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Levine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H.","family":"Gibbons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Stamler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel O.","family":"Claassen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"1235_CR1","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/S0304-3940(98)00504-7","volume":"251","author":"MG Spillantini","year":"1998","unstructured":"Spillantini MG, Crowther RA, Jakes R et al (1998) Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson\u2019s disease and dementia with Lewy bodies. 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CG is a co-founder, holds stock options, and is employed part-time by CND Life Sciences. TL is employed by CND Life Sciences and holds equity in the company. BB is also employed by CND Life Sciences. CW and DS are employees of Alterity Therapeutics and hold stock options in the company. All other authors declare no competing interests.This study was conducted independently and without commercial influence on study design, data collection, data analysis, or interpretation of results.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}