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Neuropathological studies have identified structural changes in the Purkinje cells and its connections. Recent studies additionally suggested a role of cerebellar astrocytes. Increased levels of serum glial fibrillary acidic protein (sGFAP), an astrocytic intermediate filament, were found in various neuroinflammatory and neurodegenerative diseases. The objective of this case\u2013control study was to investigate the role of sGFAP in ET focusing on early-stage late-onset patients. sGFAP was quantified by single molecule array at baseline and follow-up in 36 ET-patients (median follow-up period 5.3 years) and 36 age-matched healthy controls (4.9 years). ET-patients were assessed both at baseline and follow-up using the Fahn\u2013Tolosa\u2013Marin\u2013Tremor-Rating-Scale. The ET group was stratified (1) by median age at onset and median disease duration in early-stage late-onset and early-onset\/late-stage ET, and (2) by median sGFAP-level at baseline. Early-stage late-onset ET-patients had higher baseline-sGFAP than controls (p\u2009=\u20090.023) and higher follow-up-sGFAP and annual sGFAP-increase than both controls (p\u2009=\u20090.023; p\u2009=\u20090.007) and early-onset\/late-stage ET-patients (p\u2009=\u20090.021; p\u2009=\u20090.024). Baseline sGFAP-level correlated with tremor severity at follow-up in the early-stage late-onset (r<jats:sub>s<\/jats:sub>\u2009=\u20090.704, p\u2009=\u20090.011) but not in the early-onset\/late-stage group. Patients with high compared to low sGFAP-baseline levels had later disease onset (p\u2009&lt;\u20090.001) and sGFAP-increase was associated to tremor progression only in high sGFAP-patients (p\u2009=\u20090.041). ET-plus and pure-ET-patients did not differ in any of the sGFAP-parameters. sGFAP is elevated in early stages of late-onset ET and associated to tremor progression, substantiating the role of a neurodegenerative process in ET in this subgroup.<\/jats:p>","DOI":"10.1007\/s00702-025-02970-8","type":"journal-article","created":{"date-parts":[[2025,6,15]],"date-time":"2025-06-15T11:36:09Z","timestamp":1749987369000},"page":"1187-1195","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum glial fibrillary acidic protein is elevated in early-stage late-onset essential tremor and associated with tremor progression"],"prefix":"10.1007","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9699-2959","authenticated-orcid":false,"given":"Lukas","family":"Gattermeyer-Kell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5350-3328","authenticated-orcid":false,"given":"Michael","family":"Khalil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Kern","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7147-9037","authenticated-orcid":false,"given":"Sebastian","family":"Franthal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8403-6227","authenticated-orcid":false,"given":"Petra","family":"Katschnig-Winter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5769-6195","authenticated-orcid":false,"given":"Mariella","family":"K\u00f6gl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9725-9809","authenticated-orcid":false,"given":"Rina","family":"Demjaha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2910-3791","authenticated-orcid":false,"given":"Cansu","family":"Tafrali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edith","family":"Hofer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6406-7584","authenticated-orcid":false,"given":"Reinhold","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9764-7617","authenticated-orcid":false,"given":"Christian","family":"Enzinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3294-6824","authenticated-orcid":false,"given":"Petra","family":"Schwingenschuh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,15]]},"reference":[{"issue":"3","key":"2970_CR1","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1038\/s41582-021-00616-3","volume":"18","author":"A Abdelhak","year":"2022","unstructured":"Abdelhak A, Foschi M, Abu-Rumeileh S, Yue JK, D\u2019Anna L, Huss A, Oeckl P, Ludolph AC, Kuhle J, Petzold A, Manley GT, Green AJ, Otto M, Tumani H (2022) Blood GFAP as an emerging biomarker in brain and spinal cord disorders. 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