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Plasma Total and Phosphorylated α-Synuclein as Biomarkers in Multiple System Atrophy: A Multicenter Study
Xinrong Yuan1, Linlin Wan1,2,3,4,5, Zhao Chen1,2,3,6
1Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Current Neuropharmacology
|July 20, 2026
Summary
Plasma alpha-synuclein (α-syn) and phosphorylated alpha-synuclein (p-α-syn) show potential as biomarkers for multiple system atrophy (MSA) diagnosis and progression. Elevated levels in MSA patients correlate with autonomic dysfunction and disease advancement.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Clinical Diagnostics
Background:
- The diagnostic utility and longitudinal changes of plasma alpha-synuclein (α-syn) and phosphorylated α-synuclein (p-α-syn) in multiple system atrophy (MSA) are not fully understood.
- Accurate biomarkers are crucial for early diagnosis and monitoring of MSA progression.
Purpose of the Study:
- To investigate the potential of plasma α-syn and p-α-syn as biomarkers for the clinical diagnosis of MSA.
- To assess the role of these biomarkers in monitoring MSA disease progression and their correlation with clinical features.
Main Methods:
- Quantified plasma α-syn and p-α-syn in a cross-sectional cohort (228 MSA, 71 PD, 218 HCs) and a longitudinal cohort (101 MSA patients).
- Included an independent validation cohort (51 MSA, 52 HCs).
- Analyzed biomarker levels, diagnostic accuracy (AUC), correlation with autonomic dysfunction, and longitudinal changes.
Main Results:
- Plasma α-syn and p-α-syn levels were significantly higher in MSA patients than in healthy controls (HCs), but not different from Parkinson's disease (PD) patients.
- Both biomarkers demonstrated excellent accuracy in distinguishing MSA from HCs (AUCs: α-syn=0.932, p-α-syn=0.909), confirmed in the validation cohort.
- Elevated levels correlated with autonomic dysfunction severity; longitudinally, p-α-syn increased, and lower baseline α-syn predicted faster motor progression.
Conclusions:
- Plasma α-syn and p-α-syn show promise as supportive indicators for MSA clinical diagnosis.
- These biomarkers may aid in monitoring MSA disease progression, particularly motor decline and autonomic dysfunction.
- Dynamic changes and correlations offer insights into MSA pathophysiology and clinical management.
