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Diffusion MRI and α-Synuclein Seed Amplification Status in Parkinson's Disease
Shannon Y Chiu1, Wei-En Wang2, Robin Chen2
1Department of Neurology, Mayo Clinic College of Medicine, Scottsdale, AZ.
Annals of Neurology
|May 7, 2026
Summary
Positive alpha-synuclein seed amplification assay (SAA) in Parkinson's disease (PD) is linked to specific brain microstructural changes detected by free-water (FW) imaging. However, SAA status did not broadly differentiate diffusion MRI metrics in early PD.
Area of Science:
- Neuroimaging
- Biomarkers
- Neurodegenerative Diseases
Background:
- Positive alpha-synuclein seed amplification assay (SAA) is a key biomarker in Parkinson's disease (PD).
- Free-water (FW) imaging offers insights into brain microstructure, potentially revealing differences in early PD.
Purpose of the Study:
- To investigate if FW imaging can detect microstructural brain differences in early PD patients based on SAA status (SAA+ vs. SAA-).
- To assess the utility of FW and fractional anisotropy (FAT) in stratifying neurodegeneration in early PD.
Main Methods:
- Analysis of diffusion imaging and SAA data from the Parkinson's Progression Markers Initiative (PPMI) cohort.
- Comparison of FW and FAT metrics, along with clinical features, between SAA+ and SAA- groups.
- Application of Automated Imaging Differentiation for Parkinsonism (AIDP) to classify PD subtypes.
Main Results:
- SAA+ individuals exhibited hyposmia and shorter motor symptom duration.
- Lower FW was observed in the superior cerebellar peduncle of SAA+ individuals compared to SAA- (pFDR < 0.05).
- No significant differences in FAT were found between SAA+ and SAA- groups.
Conclusions:
- Positive SAA correlates with focal microstructural changes but not broad diffusion MRI alterations in early PD.
- Molecular confirmation of synuclein aggregation via SAA has limited ability to stratify neurodegeneration detected by FW imaging in early PD.
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