Oligodendrocyte-Myelin Dysfunction Validation in Parkinson's Disease

SUMMARY

# Oligodendrocyte-Myelin Dysfunction Validation in Parkinson's Disease ## Background and Rationale Emerging evidence suggests that oligodendrocyte dysfunction and myelin breakdown may represent primary upstream events in Parkinson's disease pathogenesis, potentially preceding alpha-synuclein aggregation and dopaminergic neurodegeneration. This clinical validation study aims to comprehensively characterize oligodendrocyte-myelin pathology in PD patients using multimodal approaches that bridge neu

METHODOLOGY NOTES

## Study Design and Patient Cohort **Phase 1: Participant Recruitment and Characterization (Months 1-6)** Recruit n=60 early-stage Parkinson's Disease patients (Hoehn-Yahr stages 1-2, disease duration <5 years, age 50-75 years) and n=60 age- and sex-matched healthy controls without neurological disease history. Implement rigorous inclusion/exclusion criteria including MRI compatibility, absence of prior stroke or demyelinating disease, and stable medication regimen for ≥3 months. Administer comprehensive clinical assessments including Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment, and olfactory testing. Collect peripheral blood samples and perform genotyping for SNCA, LRRK2, and GBA variants. Schedule baseline cognitive and motor evaluations with certified raters blinded to group assignment. ## Advanced Neuroimaging Protocol **Phase 2A: Multimodal MRI Acquisition (Months 2-8)** Perform 3T MRI imaging using standardized se