Objective: To characterize skin alpha-synuclein (α-syn) pathology in synucleinopathies as a potential tool for differential diagnosis.

Background: Differential diagnosis of PD and MSA represents a diagnostic challenge. Previous studies presented the feasibility to detect α-syn in the CSF using RT-QuIC in PD, but studies have been inconclusive in MSA. As skin RT-QuIC recently demonstrated high diagnostic accuracy for PD, we attempted to study a broader patient population that included atypical parkinsonism.

Method: We have examined 31 PD, 16 MSA, eight tauopathy (6 PSP and 2 CBD) patients, and 28 controls. The diagnosis was based on the current clinical criteria; the MSA group included patients with probable (n=6) and possible (n=8) diagnostic certainty according to the Gilman criteria. Skin biopsies were taken from the thigh, the lower back (Th10), and the neck (C7) with a punch diameter of 5 mm, half of every biopsy was used. The 100-μl RT-QuIC reaction mixture included 1 mg/mL recombinant α-syn, 500µM NaCl, 100 mM PIPES, 20µM thioflavin T (ThT) and skin biopsy lysate. The clear-bottom black microplates were incubated for 80 hours and ThT fluorescence intensity was measured every 45 minutes. Samples were considered positive if three or more replicates crossed the 10% of the maximum fluorescence threshold within the first 70 hours of incubation. Participants were considered positive if at least one of the biopsy samples was positive.

Results: Skin biopsy RT-QuIC was positive in 27 out of the 31 patients with PD, and in 14 out of 31 patients, biopsies from all locations were positive. Α-syn aggregation was detectable in 14 out of 16 MSA patients. Interestingly, half of them showed a distinctive aggregation profile with a shorter lag phase and lower total fluorescence levels, while the other half was indistinguishable from PD. 4 out of 6 patients with probable MSA, and 3 out of 8 with possible MSA had a distinct from PD aggregation profile. RT-QuIC was positive in at least one biopsy location in 4 tauopathy patients (total n=8) and 3 healthy controls (total n=28).

Conclusion: Our preliminary results show that RT-QuIC can detect α-syn aggregation in PD and MSA with high sensitivity (respectively 87% and 87,5%); the reasons for heterogeneity in the MSA cohort will be further scrutinized upon patient follow-up.

« Back to 2022 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/insights-from-skin-biopsies-%ce%b1-synuclein-real-time-quaking-induced-conversion-rt-quic-in-patients-with-parkinsons-disease-and-multiple-system-atrophy/