Objective: To determine the sensitivity and specificity of serum α-synuclein seed amplification assay (SAA) for Parkinson’s disease (PD) diagnosis in the Systemic Synuclein Sampling Study

Background: The seed amplification assay (SAA) has been shown to be valuable biomarker, demonstrating 92.6% sensitivity and 90.5% specificity in cerebrospinal fluid samples for Parkinson’s disease diagnosis[1]. However, in vivo detection of pathologic α-synuclein in PD with non-invasive methods is critical toward widespread PD biomarker testing. Initial studies have found high accuracy of serum α-synuclein SAA indicating the need for additional replication in other samples.

Method: The Systemic Synuclein Sampling Study (S4) is a multi-center, cross-sectional, observational study that evaluates abnormal α-synuclein in tissues and biofluids in PD and healthy controls (HC). All PD participants enrolled in the study had reduced dopamine transporter (DAT) binding on SPECT. In CSF, maximal fluorescence on α-synuclein SAA was used to designate subjects as +/- for CSF α-synuclein SAA. In serum, immunoprecipitation-based real-time quaking-induced conversion was performed. Serum samples will be defined as positive for α-synuclein at fluorescence intensity ≥260,000 or <260,000 or otherwise be indeterminate. Sensitivity and specificity of the serum SAA will be determined.

Results: The sample will include 57 participants with PD diagnosis (PD stage: 18 early, 20 moderate, 19 advanced), and 21 HC. Sensitivity and specific of the serum α-synuclein SAA for PD clinical diagnosis and for CSF α-synuclein SAA positivity will be reported.

Conclusion: The serum α-synuclein SAA is a promising method to detect pathologic α-synuclein noninvasively in PD. We will examine serum α-synuclein SAA sensitivity and specificity for PD diagnosis, and its relationship to CSF α-synuclein SAA, in the S4 cohort.

References: [1] Chahine LM, Beach TG, Adler CH, Hepker M, Kanthasamy A, Appel S, Pritzkow S, Pinho M, Mosovsky S, Serrano GE, Coffey C, Brumm MC, Oliveira LMA, Eberling J, Mollenhauer B; Systemic Synuclein Sampling Study. Central and peripheral α-synuclein in Parkinson disease detected by seed amplification assay. Ann Clin Transl Neurol. 2023 May;10(5):696-705. doi: 10.1002/acn3.51753. Epub 2023 Mar 27. PMID: 36972727; PMCID: PMC10187727.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/utility-of-serum-%ce%b1-synuclein-seed-amplification-assay-as-a-parkinsons-disease-biomarker/