Localized Iron Deposition and Shape Changes of Cerebellar Dentate in Progressive Supranuclear Palsy Clinical Variants.

BACKGROUND

The cerebellar dentate is a known site of iron accumulation and tau deposition in progressive supranuclear palsy (PSP); however, detailed iron distribution and localized volume and shape changes remain unclear across PSP clinical variants.

OBJECTIVE

The study aimed to clarify details about regional susceptibility distribution, volume, and shape deformation in the cerebellar dentate across PSP clinical variants.

METHODS

Sixty-seven PSP patients, including 31 PSP-Richardson syndrome, 12 PSP-parkinsonism, 10 PSP-progressive gait freezing, and 14 PSP-cortical variants (PSP-frontal, PSP-speech/language, and PSP-corticobasal syndrome), and 31 healthy controls underwent 3 Tesla magnetic resonance imaging to reconstruct quantitative susceptibility maps. Manual dentate segmentation was performed to extract magnetic susceptibility and volume adjusted for total intracranial volume. Shape deformation was assessed using Deformetrica atlas construction. Group comparisons were evaluated with Kruskal-Wallis tests and receiver operating characteristic analysis.

RESULTS

Patients with PSP-Richardson syndrome, PSP-parkinsonism, and PSP-cortical variants showed significantly increased dentate susceptibility compared with controls (P < 0.05). Patients with PSP-progressive gait freezing showed no significant susceptibility differences. Volume loss was most prominent in PSP-cortical variants, bilaterally, and PSP-Richardson syndrome, left hemisphere only (P < 0.05). Shape analysis revealed subregion-specific deformation patterns, especially in the anterior and posterior deformation in PSP-progressive gait freezing and the ventroanterior deformation in PSP-cortical variants.

CONCLUSIONS

The PSP clinical variants had different patterns of susceptibility, volume, and shape metrics, reflecting distinct neurodegenerative patterns of the cerebellar dentate. These findings contribute to our understanding of the neurobiology of PSP and may help to improve phenotypic differentiation of PSP clinical variants. © 2026 International Parkinson and Movement Disorder Society.