Citations 2
Longitudinal Dynamics of Polyglutamine‐Expanded ATXN3 in Biofluids of Spinocerebellar Ataxia Type 3
Bartfield, Jordan, Milanowski, L, Jansen‐West, Karen , Al‐Shaikh, Rana Hanna , Chmiela, Tomasz , Dunmore, Judith A. , Gorcenco, Sorina , Puschman, Andreas, Lemos, João, Januario, C, Ledoux, Mark S., Onodera, O, Aiba, I, Pfeiffer, Ronald F., Paulson, Henry, McLoughlin, Hayley S., Teive, Helio A.G., Soto-Piña, Alexandra E., Uitti, Ryan J., Strongosky, Audrey, Petrucelli, L, Paulson, Henry L. , Milanowski, Łukasz , Dunmore, Judith A , Gorcenco, Sorina , Friedman, Joseph H. , Sławek, Jarosław , Wszolek, Z.K. , Chmiela, Tomasz , Paulson, Henry L , Milanowski, Łukasz M , Gendron, Tania F. , Lemos, João , Januário, Cristina , Onodera, Osamu , Aiba, Ikuko , Pfeiffer, Ronald F. , McLoughlin, Hayley S. , Dulski, Jarosław , Sławek, Jarosław , Teive, Hélio Afonso Ghizoni , Soto‐Piña, Alexandra Estela , Uitti, Ryan J. , Strongosky, Audrey , Prudencio, Mercedes , Wszołek, Zbigniew K.
Movement Disorders | July 1, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Background Spinocerebellar ataxia type 3 (SCA3), the most common autosomal dominant ataxia, is driven by the accumulation of polyglutamine‐expanded (polyQ) ATXN3 proteins. While promising as biomarkers, their longitudinal trajectories across multiple biofluids remain poorly defined. Objectives To quantify polyQ ATXN3 levels in cerebrospinal fluid (CSF), plasma, and urine within a comprehensive cohort, utilizing serial measurements to map protein dynamics. Methods We employed a validated immunoassay to quantify polyQ ATXN3 in 97 symptomatic and 13 presymptomatic SCA3 patients, correlating levels with clinical features, ancestry, disease status, and longitudinal progression. Results Asian participants exhibited lower plasma but elevated urinary polyQ ATXN3 levels relative to other ancestries. While CSF levels were higher in symptomatic patients at baseline, they showed a significant longitudinal decline. Conclusions PolyQ ATXN3 is a viable multi‐biofluid biomarker. Declining CSF levels likely reflect neurodegeneration, supporting its role in tracking progression and emphasizing the need for ancestry‐based adjustment in trials. © 2026 International Parkinson and Movement Disorder Society.
Specific Biomarkers in Spinocerebellar Ataxia Type 3: A Systematic Review of Their Potential Uses in Disease Staging and Treatment Assessment
Soto‐Piña, Alexandra Estela , Pulido-Alvarado, Caroline C., Dulski, Jarosław , Wszołek, Zbigniew K. , Magaña, Jonathan J. , Wszolek, Z.K. , Soto-Piña, Alexandra E., Dulski, Jaroslaw
International Journal of Molecular Sciences | July 24, 2024 | Volume: 25 | Issue: 15 | Pages: 8074
Spinocerebellar ataxia type 3 (SCA3) is the most common type of disease related to poly-glutamine (polyQ) repeats. Its hallmark pathology is related to the abnormal accumulation of ataxin 3 with a longer polyQ tract (polyQ-ATXN3). However, there are other mechanisms related to SCA3 progression that require identifying trait and state biomarkers for a more accurate diagnosis and prognosis. Moreover, the identification of potential pharmacodynamic targets and assessment of therapeutic efficacy necessitates valid biomarker profiles. The aim of this review was to identify potential trait and state biomarkers and their potential value in clinical trials. Our results show that, in SCA3, there are different fluid biomarkers involved in neurodegeneration, oxidative stress, metabolism, miRNA and novel genes. However, neurofilament light chain NfL and polyQ-ATXN3 stand out as the most prevalent in body fluids and SCA3 stages. A heterogeneity analysis of NfL revealed that it may be a valuable state biomarker, particularly when measured in plasma. Nonetheless, since it could be a more beneficial approach to tracking SCA3 progression and clinical trial efficacy, it is more convenient to perform a biomarker profile evaluation than to rely on only one.