{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T12:25:33Z","timestamp":1793881533294,"version":"4.7.0"},"reference-count":60,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Therapeutic interventions in Friedreich's ataxia (FRDA) are progressing into clinical trials, and the need for robust and easily accessible biomarkers has arisen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to consolidate preliminary findings of changes in the levels of neurofilament light (NfL), glial fibrillary acidic protein (GFAP), Tau, and ubiquitin C\u2010terminal hydrolase L1(UCH\u2010L1)\u00a0in FRDA comparing two large independent cohorts of patients with healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Plasma samples of patients from two large natural history studies (n\u2009=\u2009187) and a similar sized cohort of healthy control subjects (n\u2009=\u2009127) were assessed using single\u2010molecule array measurements. Age\u2010adjusted biomarker levels were related to patients\u2019 genetic profile, clinical progression, and comorbidities, and compared with controls. Sensitivity and specificity were assessed using receiver operating characteristic analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>NfL levels were significantly elevated in patients with FRDA younger than 40\u2009years, showing a distinct age\u2010dependent trajectory: levels declined with age in FRDA but increased in controls. Longitudinal data indicated annual NfL reductions between 8% (children) and 13% (young adults &lt;\u200935\u2009years). This result is discussed in the context of other neurodegenerative conditions, with FRDA being a rare case where NfL levels decrease over time before the age of 40\u2009years. In contrast, tau was consistently elevated across all age groups in FRDA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      NfL is a sensitive biomarker in early FRDA but decreases with age, converging with control values after 35\u201340\u2009years. This age\u2010dependent pattern must be considered when interpreting the effect of interventions in clinical trials. Especially in younger (age\u2009&lt;\u200910\u2009years) or presymptomatic patients and control subjects, additional longitudinal sampling is warranted. Elevated tau levels suggest involvement in underlying disease pathophysiology. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.30250","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T10:30:04Z","timestamp":1749637804000},"page":"1863-1873","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Increase of Plasma Biomarkers in Friedreich's Ataxia: Potential Insights into Disease Pathology"],"prefix":"10.1002","volume":"40","author":[{"given":"Christian","family":"Rummey","sequence":"first","affiliation":[{"name":"Clinical Data Science GmbH  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Thomas\u2010Black","sequence":"additional","affiliation":[{"name":"The Ataxia Centre, Department of Clinical and Movement Neurosciences University College London  London United Kingdom"},{"name":"National Hospital for Neurology and Neurosurgery, University College London Hospitals Foundation NHS Trust  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector","family":"Garcia\u2010Moreno","sequence":"additional","affiliation":[{"name":"The Ataxia Centre, Department of Clinical and Movement Neurosciences University College London  London United Kingdom"},{"name":"National Hospital for Neurology and Neurosurgery, University College London Hospitals Foundation NHS Trust  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and 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