Levodopa Response Determinants in PSP — Biomarker-Guided Prediction Study

SUMMARY

# Levodopa Response Determinants in PSP — Biomarker-Guided Prediction Study ## Background and Rationale Progressive supranuclear palsy (PSP) is a tauopathy characterized by variable motor symptoms and poor levodopa responsiveness, distinguishing it from Parkinson's disease. However, clinical heterogeneity exists, with some PSP patients showing modest levodopa benefits while others demonstrate no response. This variability may reflect differences in underlying dopaminergic system integrity and pa

METHODOLOGY NOTES

Phase 1 (Weeks 1-2): Recruit 120 PSP patients meeting MDS-PSP criteria and 40 healthy controls. Obtain informed consent and perform comprehensive baseline assessments including MDS-UPDRS-III, PSP rating scale, and cognitive evaluations. Phase 2 (Weeks 3-4): Conduct DaTscan imaging using 123I-ioflupane injection (185 MBq) with SPECT acquisition 3-6 hours post-injection. Calculate striatal binding ratios using semi-automated software. Perform lumbar puncture within 7 days, collecting 15ml CSF in polypropylene tubes. Measure CSF alpha-synuclein, total tau, phospho-tau181, phospho-tau217, neurofilament light chain, and SNCA using electrochemiluminescence immunoassays. Phase 3 (Weeks 5-6): Administer standardized levodopa challenge test. Patients undergo 12-hour medication washout, then receive 250mg levodopa/25mg carbidopa. Assess UPDRS-III scores at baseline, 60, 120, and 180 minutes post-dose. Perform quantitative gait analysis and finger-tapping assessments. Phase 4 (Weeks 7-8): Statist