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ALPHA-SYNUCLEIN SEED AMPLIFICATION ASSAY IN MANIFEST AND PRODROMAL PD FROM THE LONGITUDINAL DENOPA COHORT
Abstract
Aims
Diagnostic biomarkers are most valuable in the earliest stage of Parkinson’s disease (PD). Because of the high rate of misdiagnosis, early clinical diagnosis cannot be used as gold standard to evaluate accuracy of a diagnostic test. Our goal was to determine sensitivity and specificity of the αSyn Seed Amplification Assay (αS-SAA) for manifest and prodromal PD using the longitudinal DeNoPa cohort. Thus, we compared the αS-SAA results of baseline samples (collected weeks after diagnosis) versus their 8 year clinical diagnosis.
Methods
We blindly analyzed samples from 106 PD, 26 isolated REM sleep behavior disorder (iRBD), and 64 healthy controls (HC) patients. Patients were categorized based on baseline assessment and underwent biannual clinical follow-ups at a single center. CSF samples were analyzed in triplicate, using recombinant αSyn substrate. αS-SAA conditions used in this study have been described elsewhere.
Results
Of 90 (84,9%) patients with final PD diagnosis, 85 were αS-SAA-positive (94,4% sensitivity). 16 (15,1%) initially diagnosed PD cases changed clinically to other neurological disorders during follow-up, including 2 αS-SAA-positive MSAs. 62 HC were αS-SAA-negative (96,9% specificity). 24 (92,3%) iRBD patients were αS-SAA-positive, 8 of which converted to PD during follow-up.
Conclusions
αS-SAA enables the sensitive and specific detection of misfolded αSyn in early PD and iRBD. Compared to baseline clinical assessment (plus DATSCAN in most cases), αS-SAA was 13% more specific. Remarkably, CSF from iRBDs was αS-SAA-positive up to 8 years before phenoconversion to PD.