Tau Pathology Initiation Zone Identification

SUMMARY

# Tau Pathology Initiation Zone Identification ## Background and Rationale Progressive Supranuclear Palsy (PSP) is a devastating tauopathy characterized by abnormal accumulation of 4R-tau protein in neurons and glia. While PSP presents with heterogeneous clinical phenotypes, the underlying pathological mechanisms driving disease initiation and progression remain poorly understood. Current neuropathological studies suggest that tau pathology follows stereotyped anatomical patterns, but the precis

METHODOLOGY NOTES

Phase 1 (Months 1-6): Recruit 120 PSP patients meeting MDS-PSP criteria across three phenotypes (PSP-RS n=50, PSP-P n=35, PSP-F n=35) and 40 healthy controls matched for age, sex, and education. Conduct baseline assessments including PSP Rating Scale, MoCA, Frontal Assessment Battery, and motor evaluations. Phase 2 (Months 1-30): Perform multimodal neuroimaging at baseline, 6, 12, and 24 months. Tau-PET imaging using [18F]PI-2620 (370 MBq IV injection, 90-110 minute post-injection acquisition on Siemens Biograph mCT). High-resolution 3T MRI including T1-weighted MPRAGE, T2-weighted FLAIR, and diffusion tensor imaging (64 directions, b=1000 s/mm²). Brainstem-focused sequences with 0.5mm isotropic resolution targeting midbrain and pontine nuclei. Phase 3 (Months 7-36): Image processing using FreeSurfer 7.0 for cortical parcellation, FSL for diffusion analysis, and SUVR quantification using cerebellar cortex reference region. Voxel-wise statistical analysis using SPM12, identifying region