Journal Article

FZJ-2025-05710

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dermal Alpha‐Synuclein Aggregation in Seed Amplification Assays for Parkinson's Disease Subtype Differentiation

Vieregge, M. (First author) ; Kuzkina, A. ; Janzen, A. ; Oertel, W. H. ; Sommerauer, M.FZJ* ; Volkmann, J. ; Doppler, K. (Corresponding author)

2025
Wiley-Blackwell Oxford [u.a.]

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Please use a persistent id in citations: doi:10.1111/ene.70453  doi:10.34734/FZJ-2025-05710

Abstract: 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.MethodsPatients 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.ResultsAlthough patients with clinical features of suspected body‐first PD showed slightly higher titers, significant differences were mainly observed between iRBD patients and PD patients.

Note: This work was supported by German Federal Ministry of Education and Research (BMBF). We thank Andrea Sauer-Weckertand Antonia Kohl for expert technicalassistance. Kathrin Doppler is supported by grants from theInterdisciplinary Center of Clinical Research of the University HospitalWürzburg and by the German Research Foundation as a member of theClinical Research Unit ResolvePain. Brain lysates were kindly providedby Camelia Monoranu. Michael Sommerauer receives funding from theprogram “Netzwerke 2021”, an initiative of the Ministry of Culture andScience of the State of Northrhine-Westphalia,and from the FederalMinistry of Education and Research (BMBF) within the frameworkof the funding programme ACCENT (funding code 01EO2107). OpenAccess funding enabled and organized by Projekt DEAL.

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Contributing Institute(s):

1. Kognitive Neurowissenschaften (INM-3)

Research Program(s):

1. 5252 - Brain Dysfunction and Plasticity (POF4-525) (POF4-525)

Appears in the scientific report 2025

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