Longitudinal Dynamics of Polyglutamine‐Expanded <scp>ATXN3</scp> in Biofluids of Spinocerebellar Ataxia Type 3

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.

Authors

Institutions

Publication Details

Journal
Movement Disorders
Published
2026-06-30
DOI
https://doi.org/10.1002/mds.70411
Primary Topic
Genetic Neurodegenerative Diseases
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Longitudinal Dynamics of Polyglutamine‐Expanded ATXN3 in Biofluids of Spinocerebellar Ataxia Type 3

C Januario, O Onodera, Mercedes Prudencio, Zbigniew K. Wszołek et al.
Movement Disorders
Genetic Neurodegenerative Diseases
article

Longitudinal Dynamics of Polyglutamine‐Expanded ATXN3 in Biofluids of Spinocerebellar Ataxia Type 3

C Januario, O Onodera, Mercedes Prudencio, Zbigniew K. Wszołek, Joseph H. Friedman, Andreas Puschman, Karen Jansen‐West, Judith A. Dunmore, I Aiba, Jarosław Sławek, Rana Hanna Al‐Shaikh, Jarosław Dulski, Sorina Gorcenco, L Milanowski, Tomasz Chmiela, Tania F. Gendron, Mark S. Ledoux, L Petrucelli, Alexandra E. Soto-Piña, Henry Paulson, João Lemos, Audrey Strongosky, Jordan Bartfield, Ronald F. Pfeiffer, Ryan J. Uitti, Hayley S. McLoughlin, Helio A.G. Teive
article en

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.

Movement Disorders
University of Miami (US), Oregon Health & Science University (US), Medical University of Silesia (PL), Universidad Autónoma del Estado de México (MX), Lund University (SE), Medical University of Warsaw (PL), University of Michigan (US), Jacksonville College (US), Butler Hospital (US), Copernicus Memorial Hospital (PL), Hospital de Clínicas Universidade Federal do Paraná (BR), Skåne University Hospital (SE), Mayo Clinic in Florida (US), Higashi Nagoya National Hospital (JP), Universidade Federal do Paraná (BR), Niigata University (JP), Gdańsk Medical University (PL), University of Coimbra (PT), University of Memphis (US)
Openalex Percentile: Top 10%
Genetic Neurodegenerative Diseases
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.