A rapid α-synuclein seed assay of Parkinson's disease CSF panel shows high diagnostic accuracy

Background Assays that specifically measure alpha-synuclein seeding activity in biological fluids could revolutionize the diagnosis of Parkinson's disease. Recent improvements in alpha-synuclein real-time quaking-induced conversion assays of cerebrospinal fluid have dramatically reduced reaction times from 5-13 days down to 1-2 days. Objective To test our improved assay against a panel of cerebrospinal fluid specimens from patients with Parkinson's disease and healthy controls from the MJ Fox Foundation/NINDS BioFIND collection. Methods Specimens collected from healthy controls and patients with clinically typical moderate-to-advanced Parkinson's disease were tested without prior knowledge of disease status. Correlative analyses between assay parameters and clinical measures were performed by an independent investigator. Results BioFIND samples gave positive signals in 105/108 (97%) Parkinson's disease cases versus 11/85 (13%) healthy controls. Receiver operating characteristic analyses of diagnosis of cases versus healthy controls gave areas under the curve of 95%. Beyond binary positive/negative determinations, only weak correlations were observed between various assay response parameters and Parkinson's disease clinical measures or other cerebrospinal fluid analytes. Of note, REM sleep behavioral disorder questionnaire scores correlated with the reaction times needed to reach 50% maximum fluorescence. Maximum fluorescence was inversely correlated with Unified Parkinson's Disease Rating Scale motor scores, which was driven by the patients without REM sleep behavioral disorder. Conclusions Our improved alpha-synuclein seed amplification assay dramatically reduces the time needed to diagnose Parkinson's disease while maintaining the high-performance standards associated with previous alpha-synuclein seed assays, supporting the clinical utility of this assay for Parkinson's disease diagnosis.

Automated summary

The study shows that an improved assay for diagnosing Parkinson's disease dramatically reduces the diagnosis time while maintaining high performance standards. Positive signals were found in 97% of Parkinson's disease cases compared to only 13% of healthy controls, with weak correlations between assay parameters and clinical measures observed. The assay's efficiency in diagnosing Parkinson's disease is supported by these findings.