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Dermal Alpha-Synuclein Aggregation in Seed Amplification Assays for Parkinson's Disease Subtype Differentiation
Magdalena Vieregge1, Anastasia Kuzkina1,2, Annette Janzen3
1Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
European Journal of Neurology
|November 29, 2025
Summary
Seed amplification assays in skin biopsies may help detect Parkinson's disease (PD) subtypes. However, widespread alpha-synuclein aggregation in advanced PD limits its use for differentiating subtypes.
Area of Science:
- Neurology
- Biochemistry
Background:
- Skin biopsies and seed amplification assays (SAA) detect alpha-synuclein (a-syn) aggregation in Parkinson's disease (PD).
- PD may originate in the peripheral (body-first) or central (brain-first) nervous system.
- Isolated REM sleep behavior disorder (iRBD) is a suspected premotor stage of body-first PD.
Purpose of the Study:
- Investigate if patients with suspected body-first PD exhibit higher dermal a-syn aggregation.
- Compare a-syn aggregation levels in iRBD patients versus PD patients.
Main Methods:
- Categorized patients based on clinical features.
- Analyzed SAA parameters (lag time, positive curves, titers).
- Correlated SAA parameters with clinical features.
Main Results:
- Patients with suspected body-first PD showed slightly higher a-syn titers.
- Significant differences in a-syn aggregation were mainly observed between iRBD and PD patients.
Conclusions:
- Widespread a-syn aggregation in advanced PD limits SAA utility for subtype differentiation.
- SAA in skin biopsies may be more effective in earlier disease stages or for distinguishing specific patient groups like iRBD.
