Tau PET Pattern as Therapeutic Response Predictor in 4R-Tauopathy

SUMMARY

# Tau PET Pattern as Therapeutic Response Predictor in 4R-Tauopathy ## Background and Rationale 4R-tauopathies, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), represent devastating neurodegenerative disorders characterized by accumulation of four-repeat tau protein. Despite promising preclinical results, anti-tau immunotherapies have shown variable clinical efficacy, highlighting the urgent need for biomarkers that can predict therapeutic response. Tau PET im

METHODOLOGY NOTES

Phase 1 (Months 1-6): Recruit 120 patients with clinically diagnosed 4R-tauopathy (PSP=80, CBD=40) from 6 academic medical centers. Inclusion criteria: age 45-80, disease duration 1-5 years, PSP Rating Scale 20-60. Exclusion criteria: significant cardiovascular disease, prior anti-tau therapy. Conduct baseline assessments including tau PET imaging with [18F]PI-2620 (150-300 MBq injection, 90-110 min post-injection acquisition), structural MRI, clinical rating scales, neuropsychological testing, and CSF collection for p-tau217, NfL, and inflammatory markers. Phase 2 (Months 7-12): Analyze tau PET images using FreeSurfer ROI-based analysis and voxel-wise statistical parametric mapping. Calculate cortical composite SUVR (frontal, parietal, temporal regions) and subcortical composite SUVR (brainstem, basal ganglia). Stratify patients into High-Cortical (cortical SUVR >1.5, cortical:subcortical ratio >1.2) versus Low-Cortical groups. Randomize within strata to receive either anti-tau monocl