SUMMARY
# Prodromal Parkinson's Disease Biomarker Development — Early Detection for Prevention
## Background and Rationale
This clinical study addresses the critical unmet need for reliable biomarkers to identify individuals in the prodromal phase of Parkinson's disease, before irreversible dopaminergic neuron loss occurs. Current diagnostic approaches detect PD only after 50-70% of substantia nigra neurons are lost, missing the therapeutic window where disease-modifying treatments could be most effecti
METHODOLOGY NOTES
**Phase 1: Cohort Establishment and Risk Stratification (Months 1-12)**
Recruit 1,500 participants aged 50-80 with elevated PD risk: REM sleep behavior disorder (RBD, n=400), hyposmia (n=300), genetic risk carriers (LRRK2, GBA, SNCA mutations, n=200), first-degree relatives (n=400), and age-matched controls (n=200). Implement comprehensive baseline assessment including Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), Epworth Sleepiness Scale, and University of Pennsylvania Smell Identification Test (UPSIT). Obtain genetic analysis for known PD variants and polygenic risk scores.
**Phase 2: Multimodal Biomarker Collection (Months 6-18)**
Collect CSF via lumbar puncture for α-synuclein seed amplification assay (SAA), total and phosphorylated α-synuclein, neurofilament light chain, lysosomal enzymes (GCase, cathepsin D), and neuroinflammatory markers (YKL-40, TREM2). Obtain plasma samples for α-synuclein SAA, neurofi