Several studies have confirmed α-synuclein real-time quaking-induced conversion (αSyn-RTQuIC) assay to have high sensitivity and specificity for Parkinson’s disease. However, whether
the assay can be used as a robust, quantitative measure to monitor disease progression, stratify
different synucleinopathies and predict disease conversion in patients with idiopathic REM
sleep behaviour disorder remains undetermined. The aim of this study was to assess the
diagnostic value of CSF aSyn-RT-QuIC quantitative parameters in regard to disease
progression, stratification, and conversion in synucleinopathies. We performed αSyn-RT-QuIC
in the CSF samples from 74 Parkinson’s disease, 24 multiple system atrophy and 45 idiopathic
REM sleep behaviour disorder patients alongside 55 healthy controls, analysing quantitative
assay parameters in relation to clinical data. αSyn-RT-QuIC showed 89% sensitivity and 96%
specificity for Parkinson’s disease. There was no correlation between RT-QuIC quantitative
parameters and Parkinson’s disease clinical scores (e.g. UPDRS motor) but RT-QuIC positivity
and some quantitative parameters (e.g. Vmax) differed across the different phenotype clusters.
RT-QuIC parameters also added value alongside standard clinical data in diagnosing
Parkinson’s disease. The sensitivity in multiple system atrophy was 75%, and CSF samples
showed longer T50 and lower Vmax compared to Parkinson’s disease. All RT-QuIC parameters
correlated with worse clinical progression of multiple system atrophy (e.g. change in
UMSARS). The overall sensitivity in idiopathic REM sleep behaviour disorder was 64%. In
three of the four longitudinally followed idiopathic REM sleep behaviour disorder cohorts, we
found around 90% sensitivity, but in one sample (DeNoPa) diagnosing idiopathic REM sleep
behaviour disorder earlier from the community cases, this was much lower 39%. During follow-up, 14 of 45 (31%) idiopathic REM sleep behaviour disorder patients converted to
synucleinopathy with 9/14 (64%) of convertors showing baseline RT-QuIC positivity. In
summary, our results showed that αSyn-RT-QuIC adds value in diagnosing Parkinson’s disease
and may provide a way to distinguish variations within Parkinson’s disease phenotype. The
quantitative parameters however did not correlate with disease severity in Parkinson’s disease.
The assay distinguished multiple system atrophy patients from Parkinson’s disease patients and
in contrast to Parkinson’s disease, the quantitative parameters correlated with disease
progression of multiple system atrophy. Our results also provided further evidence for αSynRT-QuIC having potential as an early biomarker detecting synucleinopathy in idiopathic REM
sleep behaviour disorder patients prior to conversion. Further analysis of longitudinally
followed idiopathic REM sleep behaviour disorder patients is needed to better understand the
relationship between αSyn-RT-QuIC signature and the progression from prodromal to different
synucleinopathies. CLICK TO REVIEW