Iron Dyshomeostasis in MSA Pathogenesis Experiment

SUMMARY

# Iron Dyshomeostasis in MSA Pathogenesis Experiment ## Background and Rationale Multiple system atrophy (MSA) is a rapidly progressive synucleinopathy with limited therapeutic options and poor prognosis. Emerging evidence suggests that iron dyshomeostasis may play a central role in MSA pathogenesis, potentially through catalyzing alpha-synuclein aggregation and promoting oxidative stress in oligodendrocytes. This comprehensive study investigates the causal relationship between iron dysregulatio

METHODOLOGY NOTES

**Phase 1: Participant Recruitment and Baseline Assessment (Months 1-6)** Recruit 120 participants: MSA patients (n=40, diagnosed per consensus criteria), Parkinson's disease controls (n=40), and healthy age-matched controls (n=40). Inclusion: age 45-75, disease duration <5 years for patient groups. Exclusion: significant iron supplementation, blood disorders, MRI contraindications. Collect comprehensive baseline data: clinical scales (UMSARS, UPDRS), cognitive assessment (MoCA), blood samples for iron studies (serum iron, ferritin, transferrin saturation, hepcidin), and advanced brain MRI including quantitative susceptibility mapping (QSM) and R2* mapping for brain iron quantification. **Phase 2: Longitudinal Monitoring and Biomarker Analysis (Months 7-18)** Conduct 6-monthly follow-up visits with repeated clinical assessments and biomarker collection. Perform detailed iron homeostasis analysis: serum hepcidin (ELISA), transferrin receptor levels, iron regulatory protein activity i