Objective: To assess the presence of oligomeric alpha-synuclein (αSyn), an early pathogenic species, in skin nerve fibers of patients with Parkinson’s disease (PD) and atypical parkinsonisms (AP), by proximity ligation assay (PLA)

Background: There is urgent need for accessible and reliable biomarkers that can stratify PD patients in clinical trials for disease-modifying therapies. Furthermore, PD and AP present overlapping clinical spectrum and are often misdiagnosed. Peripheral nervous system is involved at the early stages of PD, and phosphorylated αSyn has been detected in skin autonomic nerve fibers of PD patients

Method: We enrolled 30 idiopathic PD, 9 Multiple system atrophy (MSA), 11 AP with tauopathies (AP-TAU) and 20 age-matched healthy controls (HC). A double 3mm punch skin biopsy was performed at cervical and ankle sites and skin sections were double-stained with oligomeric αSyn-PLA and with PGP9.5, a panaxonal marker.

Results: PD and MSA patients showed higher amount of oligomeric αSyn compared to HC and AP-Tau; PD displayed it especially at the cervical site, while MSA at the ankle site. Semi-quantitative analysis revealed higher amount of co-localization signals in skin nerves in alpha-synucleinopathies, and highlighted a higher variability within PD group. The ROC curve analysis showed an accurate discrimination between PD and HC (sensitivity 77%, specificity 80%) and between PD and AP-Tau (sensitivity 82%, specificity 80%).

Conclusion: Our data provide evidence of the presence of early pathogenic species of αSyn in skin peripheral nerves of patients with PD. This finding endorses the hypothesis that skin biopsy can be used as a reliable diagnostic biomarker possibly at early stages.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alpha-synuclein-oligomers-detection-by-proximity-ligation-assay-in-skin-biopsy-is-a-biomarker-for-parkinsons-disease/