Agustin Querejeta-Coma, United Kingdom
University of Oxford Nuffield Department of Clinical NeurosciencesAuthor Of 1 Presentation
ALPHA-SYNUCLEIN RT-QUIC ASSAY AS A BIOMARKER OF DISEASE PROGRESSION AND STRATIFICATION IN PARKINSON’S DISEASE AND PREDICTING DISEASE CONVERSION FROM RBD
Abstract
Aims
Several studies have confirmed alpha-synuclein (aSyn) real-time quaking-induced conversion (RT-QuIC) assay to have high sensitivity and specificity for Lewy body disorders. Here, we study less understood robustness and reproducibility of the assay as well as its use as a quantitative measure to monitor disease progression, stratifying between different synucleinopathies and predicting disease conversion in idiopathic RBD (iRBD).
Methods
We performed aSyn RT-QuIC in 93 cerebrospinal fluid (CSF) samples from longitudinally followed Parkinson’s disease (PD) patients and controls and examined how quantitative readouts extrapolated from the assay correlated with clinical symptoms. We also examined CSF from 23 longitudinally followed MSA patients and 45 polysomnographically verified iRBD patients derived from four different cohorts.
Results
aSyn RT-QuIC showed 89% sensitivity and 94% specificity for PD. None of the assay parameters correlated with clinical symptoms but Vmax across the different phenotype clusters differed significantly (p=0.018). Adding any of the assay parameters to the logistic regression model of PD vs. control with the MDS prodromal PD score showed strong association with PD status. The sensitivity in our MSA samples was 74% and MSA CSF showed longer T50 and significantly lower Vmax and Max Fluorescence compared to PD. The sensitivity between different RBD cohorts varied from 39% to 91%, probably representing how close the patients are to disease conversion.
Conclusions
aSyn RT-QuIC adds value in diagnosing PD but the quantitative data does not correlate to disease severity. This assay can clearly distinguish MSA patients and could identify prodromal subjects with iRBD and risk of conversion.