Objective: The main objective is to evaluate the sensitivity of aSyn-RT-QuIC in diagnosing Parkinson’s Disease (PD) from non-invasive saliva. The results will be corroborated in plasma and CSF.

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Background: PD is an age-related neurodegenerative disorder worldwide. Its natural history is very heterogeneous which mostly results in inaccurate clinical diagnosis. Each patient behaves differently. The amount of dopamine in PD is reduced below 70-80% leading to bradykinesia, tremors, rigidity, postural instability, and cognitive, and psychiatric symptoms. Till today there is no validated biomarker to diagnose it. RT-QuIC assay has been developed for alpha-synuclein (aSyn) seeds in CSF and skin biopsy, making it a sensitive diagnostic tool for PD. However, collecting CSF and skin biopsy involves health-related risks in patients.

Method: The main objectives will be to evaluate aSyn-RT-QuIC assays in PD diagnosis from non-invasive saliva of PD, Parkinsonism, other neurodegenerative disorders (ND), and non-ND controls. The results will be corroborated in plasma and CSF of PD, Parkinsonism, other ND and non-ND, and healthy controls. Statistical analysis will be performed to determine the sensitivity and accuracy of the RT-QuIC PD test. The initial pilot study funded by DHR (MoH&FW), will select a group of individuals with clinically diagnosed PD (n=80), Parkinsonism, and other neurodegenerative disorders (n=40), and non-neurological healthy controls (n=40).

Results: We will perform RT-QuIC assays to detect misfolded alpha-synuclein (aSyn) protein, which can be an early sign of PD. Misfolded aSyn protein recruits monomeric aSyn into newly formed fibrils as detected by thioflavin T fluorescence. We will test the sensitivity and accuracy of aSyn-RTQuIC in diagnosing PD. We will also check if individuals who test positive for saliva-aSyn are associated with a specific clinical presentation, disease stage, or disease course. We will perform a statistical analysis to evaluate our findings.

Conclusion: We will test RT-QuIC assays from a greater number of samples. This test may help in sensitive, cost-effective, accurate, early detection and progressive monitoring of PD synucleopathies.

References: Adler, C. H., Beach, T. G., Zhang, N., Shill, H. A., Driver-Dunckley, E., Mehta, S. H., … & Belden, C. M. (2021). Clinical diagnostic accuracy of early/advanced Parkinson disease: an updated clinicopathologic study. Neurology: Clinical Practice, 11(4), e414-e421.

Bentivenga, G. M., Mammana, A., Baiardi, S., Rossi, M., Ticca, A., Magliocchetti, F., … & Parchi, P. (2024). Performance of a seed amplification assay for misfolded alpha-synuclein in cerebrospinal fluid and brain tissue in relation to Lewy body disease stage and pathology burden. Acta Neuropathologica, 147(1), 18.

Cersósimo, M. G., Perandones, C., Micheli, F. E., Raina, G. B., Beron, A. M., Nasswetter, G., … & Benarroch, E. E. (2011). Alpha‐synuclein immunoreactivity in minor salivary gland biopsies of Parkinson’s disease patients. Movement Disorders, 26(1), 188-190.

Chahine, L. M., Beach, T. G., Adler, C. H., Hepker, M., Kanthasamy, A., Appel, S., … & Caspell‐Garcia, C. (2023). Central and peripheral α‐synuclein in Parkinson disease detected by seed amplification assay. Annals of clinical and translational neurology, 10(5), 696-705.

Siderowf, A., Concha-Marambio, L., Lafontant, D. E., Farris, C. M., Ma, Y., Urenia, P. A., … & Soto, C. (2023). Assessment of heterogeneity among participants in the Parkinson’s Progression Markers Initiative cohort using α-synuclein seed amplification: a cross-sectional study. The Lancet Neurology, 22(5), 407-417.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alpha-synuclein-amplification-assays-utilizing-real-time-quaking-induced-conversion-rt-quic-from-non-invasive-saliva-as-a-novel-diagnostic-tool-for-patients-with-parkinsons-disease/