Choroid plexus enlargement correlated with motor dysfunction in spinocerebellar ataxia type 3

To investigate Choroid plexus (CP) structural changes using multimodal MRI, and assess the correlation between CP damage and motor dysfunction in SCA3 patients.

We prospectively recruited 64 SCA3 patients and 50 age- and sex-matched healthy controls (HCs). CP volume (CPV) and other brain regions were measured using FreeSurfer 7.3, while free-water (FW) imaging metrics were analyzed with FSL. We compared the differences in CPV and FW imaging metrics among the pre-symptomatic SCA3 group, symptomatic SCA3 group, and HC group. Partial correlation, structural equation modeling, and multivariate regression explored the relationships among CPV, CAG repeats, brain structures, and motor scales.

CPV, FW, and Freewater-corrected Anisotropy (FAt) were significantly increased in symptomatic SCA3 patients compared to HCs and pre-symptomatic patients. CPV was positively correlated with CAG repeats, CSF volume, motor impairment and negatively correlated with cerebellar and brainstem volumes. Structural equation modeling revealed that CPV mediated the effect of CAG repeats on motor function by influencing CSF volume. CP and brainstem volumes were independent predictors of motor function and could distinguish pre-symptomatic from symptomatic patients.

This study first demonstrates that CP enlargement is a novel biomarker of motor dysfunction in SCA3. The CP may be involved in the pathogenesis of SCA3 by affecting CSF circulation and brain homeostasis. Targeting the CP could be a potential therapeutic strategy for SCA3. Clinical trials registration [www.

gov], identifier [ChiCTR1800019901].