Objective: To investigate the proficiency of RT-QuIC in detecting the presence of misfolded α-synuclein (α-syn) on the olfactory mucosa (OM) and CSF of patients with a clinical diagnosis of Parkinson’s disease (PD) and other synucleinopathies.

Background: Biomarkers enabling early recognition of PD are urgently needed. PD, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are characterized by misfolding and aggregation of pathological α-syn. Real-time quaking-induced conversion (RT-QuIC) is able to detect misfolded α-syn in CSF and other peripheral tissues of patients with α-synucleinopathies, and might be included in the future diagnostic criteria.

Method: We obtained OM and CSF samples from a cohort of 53 patients. 37 patients (SYN group) had a diagnosis of PD (29), DLB (4), and MSA (4); the remaining 16 patients had other neurodegenerative diseases and were included in the non-SYN group.

OM samples were collected through nasal swab in 45 patients; CSF was obtained through lumbar puncture in 42 patients; 34 patients underwent both procedures.

Samples were analyzed at the University of Verona (Department of Neurosciences, Biomedicine, and Movement Science); RT-QuIC was used to assess the presence of pathological α-syn seeding activity. Sensitivity and specificity values were calculated for both OM and CSF RT-QuIC.

Results: RT-QuIC sensitivity in the detection of α-syn on OM was 75.8%, while specificity resulted 91.7%. When we analyzed only the PD subgroup we found a higher sensitivity of OM RT-QuIC (81.5%).

CSF RT-QuIC gave similar results, with 85.2% sensitivity and 80.0% specificity. The subgroup analysis among PD patients yielded to higher sensitivity values (95.0%).

Finally, combining the results of both OM and CSF RT-QuIC, we obtained a sensitivity value of 91.3% in detecting misfolded α-syn, with a true negative rate of 90.9%. Remarkably, all of the 18 PD patients who underwent both analyses (CSF and OM) resulted positive for the presence of pathological α-syn on CSF, OM or both.

Conclusion: RT-QuIC performed on CSF and OM has high sensitivity in the detection of pathological α-syn. The assay performed on CSF and OM gave comparable results, the latter being less invasive for patients. Finally, we highlight that the combination of OM and CSF analyses may improve diagnostic accuracy especially in PD patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/rt-quic-for-detection-of-pathological-%ce%b1-synuclein-in-the-olfactory-mucosa-and-csf-of-parkinsons-disease-patients/