Synaptic Density Reductions in MSA: A Potential Biomarker Identified Through [18F]SynVesT-1 PET Imaging
Jian Li1, Daji Chen2, Yongxiang Tang1
1Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Annals of Neurology
|January 20, 2025
Summary
Multiple system atrophy (MSA) shows widespread synaptic density loss, especially in the basal ganglia and infratentorial regions. [18F]SynVesT-1 PET imaging can help diagnose MSA and monitor disease severity.
Area of Science:
- Neuroscience
- Radiology
- Biomarker Discovery
Background:
- Multiple system atrophy (MSA) is a progressive neurodegenerative disorder.
- Accurate diagnosis and monitoring of disease severity in MSA remain challenging.
- Synaptic dysfunction is a key pathological feature in MSA.
Purpose of the Study:
- To assess synaptic density alterations in patients with MSA using [18F]SynVesT-1 positron emission tomography/computed tomography (PET/CT).
- To evaluate the potential of [18F]SynVesT-1 PET/CT as a biomarker for MSA diagnosis and disease severity.
- To differentiate between MSA subtypes (MSA-P and MSA-C) and Parkinson's disease (PD) based on synaptic density patterns.
Main Methods:
- Prospective study involving 60 MSA patients (30 MSA-P, 30 MSA-C), 30 PD patients, and 30 healthy controls (HCs).
- All participants underwent [18F]SynVesT-1 PET/CT imaging for synaptic density assessment.
- Visual, voxel, and region of interest (VOI) analyses were performed, with diagnostic performance evaluated by receiver operating characteristic (ROC) analysis. Spearman correlation assessed the relationship between synaptic density and disease severity.
Main Results:
- Patients with MSA exhibited significant reductions in synaptic density across multiple brain regions, including the cerebellum, putamen, medulla oblongata, ventral tegmental area, and pons.
- MSA-C patients showed marked cerebellar synaptic loss, while MSA-P patients had significant synaptic loss in the posterior putamen.
- MSA patients displayed more pronounced infratentorial synaptic density reduction compared to PD patients. VOI-based analysis significantly outperformed visual assessment for MSA diagnosis and subtype differentiation.
- Brain synaptic density correlated significantly with motor function scales in MSA patients.
Conclusions:
- Widespread synaptic density reductions are characteristic of MSA, particularly in the basal ganglia and infratentorial areas.
- [18F]SynVesT-1 PET/CT shows promise as a biomarker for diagnosing MSA and assessing disease progression.
- This imaging technique could guide future synaptic restoration therapies in MSA.
