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Vieregge, M.* ; Kuzkina, A.* ; Janzen, A.* ; Oertel, W.H. ; Sommerauer, M.* ; Volkmann, J.* ; Doppler, K.*

Dermal alpha-synuclein aggregation in seed amplification assays for parkinson's disease subtype differentiation.

Eur. J. Neurol. 32:e70453 (2025)

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BACKGROUND: Skin biopsies and seed amplification assays (SAA) provide a sensitive and potentially quantitative method to detect alpha-synuclein (a-syn) aggregation in peripheral nerve fibers in Parkinson's disease (PD). Relating to the previously published hypothesis that PD may either originate in the peripheral (body-first) or central (brain-first) nervous system, we investigated whether patients with clinical features that have been reported to be associated with a suspected body-first subtype of PD exhibit higher levels of a-syn aggregation in dermal nerve fibers compared to those without these features. Patients with isolated REM sleep behavior disorder (iRBD) representing a suspected premotor stage of body-first PD were studied in comparison to the PD cohort. METHODS: Patients were categorized on the basis of clinical features, and SAA parameters such as lag time, number of positive curves, and titers were analyzed and correlated with clinical features. RESULTS: Although patients with clinical features of suspected body-first PD showed slightly higher titers, significant differences were mainly observed between iRBD patients and PD patients. CONCLUSIONS: Our data suggest that widespread α-syn aggregation in advanced PD limits the use of SAA in skin biopsies for subtype differentiation.

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