Abstract
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.
Results
We first looked at potential demographic differences between PPMI and PDBP repositories and found no statistical differences in age, race, or ethnicity apart from race and gender for the control cohort comparison (Table 1). To verify the PDBP and PPMI cohorts’ comparability in terms of symptomology, United Parkinson’s Disease Rating Scale (UPDRS) data were analyzed; there were no statistical differences between repositories (Table 1, Fig. 2).
An important difference between these repositories is the inclusion criteria, which includes DAT-SPECT in the PPMI cohort. Considering repository diagnosis as the comparator, αSyn-SAA accuracy was higher in the PPMI cohort (93.6%) than in the PDBP cohort (83.9%) (Table 2). It is important to note that the error rate for SAA using the PPMI cohort was 6.4% compared to 16.1% in the PDBP cohort (p 0.045) (Table 2). For information, additional validation results, including analytical validation and specimen stability studies, are shown in the Online Resource.
View Full Article: https://link.springer.com/article/10.1007/s00415-023-11810-2
DOI: https://doi.org/10.1007/s00415-023-11810-2