SUMMARY
# Axonal Transport Dysfunction Validation in Parkinson's Disease
## Background and Rationale
Axonal transport dysfunction represents a potentially critical upstream mechanism in Parkinson's disease (PD) pathogenesis, preceding the classical motor symptoms and dopaminergic cell loss. This clinical validation study seeks to establish axonal transport dysfunction as an early biomarker and therapeutic target by examining multiple complementary readouts in PD patients across disease stages. The exper
METHODOLOGY NOTES
**Study Design and Participant Recruitment**
This prospective longitudinal clinical validation study enrolls 200 Parkinson's Disease patients (100 early-stage: Hoehn-Yahr stages 1-2; 100 mid-stage: stages 2.5-3) and 100 age-matched healthy controls (HC) stratified by age decade (50-60, 60-70, 70-80 years). PD diagnosis follows Movement Disorder Society criteria with confirmed dopaminergic deficit on DAT-SPECT imaging. Exclusion criteria include secondary parkinsonism, prior neurosurgical intervention, MRI contraindications, or significant cerebrovascular disease. Participants undergo baseline assessments including Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment, and comprehensive medication inventories with washout protocols for dopaminergic agents (12-hour minimum) before testing.
**Advanced Neuroimaging Protocol**
High-field 3T MRI with echo-planar diffusion imaging acquires 64-direction diffusion-weighted sequences (b=1000, 2000, 3000 s/mm²) with 2mm