Disease-associated aggregated alpha-synuclein was found in peripheral tissues in PD, including skin. RT-QuIC-based αSyn-SAA with CSF had high sensitivity and specificity for PD diagnosis in prior studies, but skin offers a less invasive and more easily accessible tissue.

Following written informed consent, we obtained skin punch biopsies from 158 living participants; 95 with PD (21 possible PD and 74 probable PD, by UK Brain Bank criteria), 17 other synucleinopathies (8 DLB and 9 MSA), and 46 controls.  Bilateral 4mm biopsies were lateral to the C7 vertebra except for 6 subjects biopsied 15cm above the patella. Endpoint Thioflavin T fluorescence values (ThT), a measure of αSyn-seeding activity in RT-QuIC, was measured. Using an optimal ThT cutoff of 64,750, assay sensitivity and specificity values were calculated for each sub-group.  Welch 2-sample t-test was used to compare mean age and Chi-Squared Test to compare percentage of females.  

In PD versus controls, mean(SD) age was 69.41(9.11) versus 66.39(8.53) (p=0.057) and percentage of females was 42.11% versus 69.56% (p=0.004). In PD, median Hoehn&Yahr score (N=94) was 2.0, mean(SD) MDS-UPDRS Part 3 (N=93) was 32.04(10.92) and total MDS-UPDRS (N=93) was 50.82(19.02). 3/46 of the controls were positive by the biopsy skin αSyn-SAA (or SAA⁺), corresponding to 93.5% specificity. In comparison, 82.1% (78/95) of PD cases and 82.4% (14/17) of non-PD parkinsonism cases were SAA⁺.  Sensitivity was 85.1% in probable PD as opposed to 71.4% in possible PD.