Christian Rummey, Gilbert Thomas-Black, Hector Garcia-Moreno, David R Lynch, Rosella Abeti, Huseyin Arisoy, Amanda Heslegrave, Henrik Zetterberg, Paola Giunti
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{"title":"血浆生物标志物在弗里德赖希共济失调中的增加:对疾病病理学的潜在见解。","authors":"Christian Rummey, Gilbert Thomas-Black, Hector Garcia-Moreno, David R Lynch, Rosella Abeti, Huseyin Arisoy, Amanda Heslegrave, Henrik Zetterberg, Paola Giunti","doi":"10.1002/mds.30250","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Therapeutic interventions in Friedreich's ataxia (FRDA) are progressing into clinical trials, and the need for robust and easily accessible biomarkers has arisen.</p><p><strong>Objective: </strong>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-terminal hydrolase L1(UCH-L1) in FRDA comparing two large independent cohorts of patients with healthy controls.</p><p><strong>Methods: </strong>Plasma samples of patients from two large natural history studies (n = 187) and a similar sized cohort of healthy control subjects (n = 127) were assessed using single-molecule array measurements. Age-adjusted biomarker levels were related to patients' genetic profile, clinical progression, and comorbidities, and compared with controls. Sensitivity and specificity were assessed using receiver operating characteristic analyses.</p><p><strong>Results: </strong>NfL levels were significantly elevated in patients with FRDA younger than 40 years, showing a distinct age-dependent trajectory: levels declined with age in FRDA but increased in controls. Longitudinal data indicated annual NfL reductions between 8% (children) and 13% (young adults < 35 years). 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 years. In contrast, tau was consistently elevated across all age groups in FRDA.</p><p><strong>Conclusions: </strong>NfL is a sensitive biomarker in early FRDA but decreases with age, converging with control values after 35-40 years. This age-dependent pattern must be considered when interpreting the effect of interventions in clinical trials. Especially in younger (age < 10 years) or presymptomatic patients and control subjects, additional longitudinal sampling is warranted. Elevated tau levels suggest involvement in underlying disease pathophysiology. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":520713,"journal":{"name":"Movement disorders : official journal of the Movement Disorder Society","volume":" ","pages":""},"PeriodicalIF":7.6000,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Increase of Plasma Biomarkers in Friedreich's Ataxia: Potential Insights into Disease Pathology.\",\"authors\":\"Christian Rummey, Gilbert Thomas-Black, Hector Garcia-Moreno, David R Lynch, Rosella Abeti, Huseyin Arisoy, Amanda Heslegrave, Henrik Zetterberg, Paola Giunti\",\"doi\":\"10.1002/mds.30250\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Therapeutic interventions in Friedreich's ataxia (FRDA) are progressing into clinical trials, and the need for robust and easily accessible biomarkers has arisen.</p><p><strong>Objective: </strong>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-terminal hydrolase L1(UCH-L1) in FRDA comparing two large independent cohorts of patients with healthy controls.</p><p><strong>Methods: </strong>Plasma samples of patients from two large natural history studies (n = 187) and a similar sized cohort of healthy control subjects (n = 127) were assessed using single-molecule array measurements. Age-adjusted biomarker levels were related to patients' genetic profile, clinical progression, and comorbidities, and compared with controls. Sensitivity and specificity were assessed using receiver operating characteristic analyses.</p><p><strong>Results: </strong>NfL levels were significantly elevated in patients with FRDA younger than 40 years, showing a distinct age-dependent trajectory: levels declined with age in FRDA but increased in controls. Longitudinal data indicated annual NfL reductions between 8% (children) and 13% (young adults < 35 years). 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 years. In contrast, tau was consistently elevated across all age groups in FRDA.</p><p><strong>Conclusions: </strong>NfL is a sensitive biomarker in early FRDA but decreases with age, converging with control values after 35-40 years. This age-dependent pattern must be considered when interpreting the effect of interventions in clinical trials. Especially in younger (age < 10 years) or presymptomatic patients and control subjects, additional longitudinal sampling is warranted. Elevated tau levels suggest involvement in underlying disease pathophysiology. © 2025 The Author(s). 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Increase of Plasma Biomarkers in Friedreich's Ataxia: Potential Insights into Disease Pathology.
Background: Therapeutic interventions in Friedreich's ataxia (FRDA) are progressing into clinical trials, and the need for robust and easily accessible biomarkers has arisen.
Objective: 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-terminal hydrolase L1(UCH-L1) in FRDA comparing two large independent cohorts of patients with healthy controls.
Methods: Plasma samples of patients from two large natural history studies (n = 187) and a similar sized cohort of healthy control subjects (n = 127) were assessed using single-molecule array measurements. Age-adjusted biomarker levels were related to patients' genetic profile, clinical progression, and comorbidities, and compared with controls. Sensitivity and specificity were assessed using receiver operating characteristic analyses.
Results: NfL levels were significantly elevated in patients with FRDA younger than 40 years, showing a distinct age-dependent trajectory: levels declined with age in FRDA but increased in controls. Longitudinal data indicated annual NfL reductions between 8% (children) and 13% (young adults < 35 years). 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 years. In contrast, tau was consistently elevated across all age groups in FRDA.
Conclusions: NfL is a sensitive biomarker in early FRDA but decreases with age, converging with control values after 35-40 years. This age-dependent pattern must be considered when interpreting the effect of interventions in clinical trials. Especially in younger (age < 10 years) or presymptomatic patients and control subjects, additional longitudinal sampling is warranted. Elevated tau levels suggest involvement in underlying disease pathophysiology. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.