Seed amplification assay results illustrate discrepancy in Parkinson’s disease clinical diagnostic accuracy and error rates

• Published in: Journal of neurology Vol. 270; no. 12; pp. 5813 - 5818
• Main Authors: Middleton, John Stephen, Hovren, Hanna Lynn, Kha, Nelson, Medina, Manuel Joseph, MacLeod, Karen Ruth, Concha-Marambio, Luis, Jensen, Kendal Jay
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2023; Springer Nature B.V
• Subjects: Accuracy; alpha-Synuclein - cerebrospinal fluid; Basal ganglia; Central nervous system diseases; Cerebrospinal fluid; Computed tomography; Diagnosis; Discordance; Dopamine; Dopamine transporter; Humans; Medicine; Medicine & Public Health; Movement disorders; Neurodegenerative diseases; Neurology; Neuroradiology; Neurosciences; Original Communication; Parkinson Disease - cerebrospinal fluid; Parkinson Disease - diagnostic imaging; Parkinson's disease; Parkinsonian Disorders; Single photon emission computed tomography; Statistical analysis; Symbiosis; Synuclein; α-Synuclein; Seed amplification; Synucleinopathy; Parkinson’s disease
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-023-11810-2

Parkinson’s disease (PD) may be misdiagnosed due to the clinical overlap between PD and atypical parkinsonism. The utility of α-Synuclein (αSyn) Seed Amplification Assay (SAA) as a diagnostic indicator for PD has been reported in numerous studies, but never when administered as a validated clinical laboratory test. This study compares results from αSyn-SAA validation testing performed using well-characterized cohorts from two biorepositories to better understand the accuracy of PD clinical diagnosis. Blinded cerebrospinal fluid (CSF) specimens from a repository that included cohorts of subjects clinically diagnosed as PD or healthy controls, both with confirmatory dopamine transporter single-photon emission computed tomography (DAT SPECT) imaging, and blinded CSF specimens from a repository that included cohorts of subjects clinically diagnosed as PD or healthy controls based on clinical diagnosis alone, were tested as part of the validation studies for the diagnostic αSyn-SAA test (SYNTap® Biomarker Test). Measured αSyn-SAA test accuracy was 83.9% using clinical diagnosis as comparator, and 93.6% using clinical diagnosis with confirmatory DAT- SPECT imaging as comparator. The statistically significant discordance between accuracy determinations using specimens classified using different diagnostic inclusion criteria indicates that there is some symbiosis between dopamine-weighted imaging and αSyn-SAA results, both of which are associated with higher accuracy compared with the clinical diagnosis alone.