Objective: To present an overview of the Progressive Supranuclear Palsy Neuroimage Initiative (PSPNI) from China.

Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease with significant clinical heterogeneity. Natural history data and objective biomarkers for distinct phenotypes remain scarce, particularly in the Chinese population. PSPNI was established to address these gaps through a longitudinal and multimodal framework.

Method: PSPNI is an ongoing, single-center, prospective, observational study. Participants fulfilling the 2017 Movement Disorder Society criteria are consecutively recruited from Huashan Hospital, Fudan University, Shanghai, China. Multi-dimensional data, including comprehensive clinical evaluation, multimodal neuroimaging (brain magnetic resonance imaging, ¹⁸F-Florzolotau positron emission tomography [PET], dopamine transporter PET, and ¹⁸F-FDG PET), and biomaterials, are collected at baseline and annual follow-ups. The study endpoint is a composite outcome of death or loss of independence. Survival analysis was performed using the Kaplan-Meier method and the log-rank test, with the date of censoring set at 31 Dec 2025.

Results: Between Oct 2018 and Apr 2025, 396 patients were enrolled (age 67 [61, 71] years; 46.2% female; disease duration 2.9 [2.0, 4.5] years): 223 with PSP-Richardson syndrome (PSP-RS), 121 with PSP-subcortical, and 52 with PSP-cortical. Based on a subcohort of 148 patients, we established an ¹⁸F-Florzolotau PET staging system and a visual reading algorithm for PSP diagnosis. Furthermore, two subtypes with distinct spatiotemporal tau progression trajectories were identified using the Subtype/Stage Inference algorithm. As of Dec 2025, 155 patients had completed ≥1 follow-up clinical visit (median follow-up 2.2 [1.5, 3.6] years), while 84 reached the study endpoint. The median survival time since symptom onset was 10.1 years for the full cohort, with significantly shorter survival in PSP-RS and PSP-cortical compared to PSP-subcortical (both P_FDR<0.005).

Conclusion: PSPNI encompasses a broad phenotypic spectrum of PSP, including both PSP-RS and variant PSP. Through a multimodal longitudinal framework, PSPNI will provide a comprehensive natural history dataset of Chinese PSP patients and facilitate the exploration of biomarkers for early diagnosis and disease monitoring.

References: 1. Liu F-T, Lu J-Y, Li X-Y, et al. Visual reading for [18F]Florzolotau Tau PET scans in progressive supranuclear palsy. Eur J Nucl Med Mol Imaging. https://doi.org/10.1007/s00259-024-06923-3
2. Liu F-T, Lu J-Y, Li X-Y, et al. 18F-Florzolotau PET imaging captures the distribution patterns and regional vulnerability of tau pathology in progressive supranuclear palsy. Eur J Nucl Med Mol Imaging 2023;50(5):1395–1405. https://doi.org/10.1007/s00259-022-06104-0
3. Hong J, Lu J, Liu F, et al. Uncovering distinct progression patterns of tau deposition in progressive supranuclear palsy using [18F]Florzolotau PET imaging and subtype/stage inference algorithm. eBioMedicine 2023;97:104835. https://doi.org/10.1016/j.ebiom.2023.104835

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-multimodal-biomarker-profiles-in-progressive-supranuclear-palsy-the-pspni-cohort-study-in-china/