SUMMARY
# Non-Dopaminergic Neurotransmitter Degeneration in PD - Experiment Design
## Background and Rationale
This comprehensive study challenges the traditional dopamine-centric view of Parkinson's disease by systematically investigating the temporal sequence and clinical impact of non-dopaminergic neurotransmitter system degeneration. Growing evidence suggests that noradrenergic, serotonergic, cholinergic, and GABAergic systems may be affected early in PD pathogenesis, potentially driving many non-mo
METHODOLOGY NOTES
## **Phase 1: Cross-Sectional Neurochemical Mapping (Months 1-12)**
Recruit 200 PD patients across disease stages (50 each: de novo, early [H&Y 1-2], moderate [H&Y 3], advanced [H&Y 4-5]) and 50 age-matched controls from 6 movement disorder centers. Perform comprehensive neurotransmitter system mapping using PET imaging: [11C]MeNER for noradrenaline transporter, [11C]DASB for serotonin transporter, [18F]FEOBV for vesicular acetylcholine transporter, and [11F]flumazenil for GABA-A receptors. Conduct DaTscan SPECT for dopamine transporter reference. Measure plasma and CSF neurotransmitter metabolites: MHPG (noradrenaline), 5-HIAA (serotonin), choline (acetylcholine), and GABA levels using HPLC-MS/MS.
## **Phase 2: Longitudinal Progression Tracking (Months 6-48)**
Follow cohort with annual PET imaging and clinical assessments over 4 years. Primary clinical measures: MDS-UPDRS (motor and non-motor), cognitive assessment battery (attention, executive function, memory), sleep studies (polys