To determine sensitivity and specificity of skin RT-QuIC for disease-associated alpha-synuclein (αSyn^D) in Parkinson disease (PD) compared to age-matched controls.  

Following written informed consent, we obtained skin punch biopsies from 39 living subjects with PD and 11 age-matched controls.  Thioflavin T fluorescence endpoint (ThT), a measure of αSyn-seeding activity on RT-QuIC, was assessed. Correlation between ThT and PD severity was determined (Spearman’s rho).  ROC analysis was conducted with PD status using ThT, allowing calculation of assay sensitivity and specificity.  

In PD versus controls, mean age (66.79 versus 64.09;p=0.159), mean MoCA (27.41 versus 27.27;p=0.981 2-sided Fisher's Exact Test), and gender (41.0% versus 54.5% female;p=0.503 2-sided Fisher's Exact Test) were not significantly different.  In PD subjects, mean(SD) MDS-UPDRS was 48.72(21.04), MDS-UPDRS PartIII was 29.59(11.42), and median(IQR) modified Hoehn&Yahr was 2.00(0.5), none of which significantly correlated with ThT.  Mean±SD ThT was 51.9%±24% (PD) versus 29.8%±5.3% (control);p=0.008 Mann-Whitney U Test.  Based on ROC analysis, AUC was 0.762. With positive ThT defined as ≥36.44%, based on ROC curve, ThT positivity was higher in PD (p=0.002 Fisher’s exact test).  ThT≥36.44% had a specificity of 91% for PD and a sensitivity of 64%.  

Our RT-QuIC assay for skin αSyn^D differentiated PD from controls, with moderate sensitivity and high specificity.  There is a possibility, based on prior experience in PD and prion disease, that sensitivity of this assay will improve with analysis of multiple tissue samples per subject, increase in sample size, and adjustment of tissue handling and assay parameters. Larger sample sizes will also be needed to better determine whether this assay can be utilized as a biomarker for PD severity.