PSP and CBS Biomarker Validation Study

SUMMARY

# PSP and CBS Biomarker Validation Study ## Background and Rationale Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS) are devastating 4R-tauopathies that present with overlapping clinical features, making early and accurate diagnosis extremely challenging. Current diagnostic approaches rely primarily on clinical criteria, often leading to misdiagnosis rates exceeding 30% and delayed therapeutic interventions. The lack of validated biomarkers significantly hampers clinical tri

METHODOLOGY NOTES

Phase 1 (Months 1-6): Recruit 300 participants across 5 centers: 75 PSP patients (MDS-PSP criteria), 75 CBS patients (Armstrong criteria), 75 PD controls, 75 healthy controls. Obtain informed consent, medical history, and baseline assessments including MDS-UPDRS, PSP Rating Scale, and cognitive batteries. Phase 2 (Months 1-24): Collect biospecimens at baseline, 6, 12, 18, and 24 months. CSF collection (20mL) via lumbar puncture with immediate processing and storage at -80°C. Plasma collection (50mL) with EDTA tubes, centrifugation within 2 hours, and aliquoting. Perform neuroimaging at baseline, 12, and 24 months using standardized protocols: 3T MRI with T1-weighted, FLAIR, DTI sequences, and tau-PET with [18F]MK-6240 tracer. Phase 3 (Months 6-30): Biomarker analysis using established and novel assays. CSF analysis via Simoa and ELISA for tau isoforms (AT8, AT180, AT270 phospho-epitopes), NFL, GFAP, and targeted proteomics panel. Plasma analysis using ultra-sensitive Simoa assays for p