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Updated: Jul 2, 2026
A Simple Composite Phenotype Scoring System for Evaluating Mouse Models of Cerebellar Ataxia
Published on: May 21, 2010
Longitudinal Dynamics of Polyglutamine-Expanded ATXN3 in Biofluids of Spinocerebellar Ataxia Type 3
Jordan Bartfield1, Lukasz Milanowski2,3, Karen R Jansen-West1,4
1Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
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.
