Diagnostic value of cerebrospinal fluid alpha-synuclein seed quantification in synucleinopathies

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Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

Candidate categories

none

Consensus categories

none

Domain

Candidate signal: noneConsensus signal: none

Study design

Candidate signal: ObservationalConsensus signal: none

Genre

Candidate signal: EmpiricalConsensus signal: Empirical

Teacher disagreement score

0.509

Threshold uncertainty score

0.530

Validation status

machine_predicted_unvalidated · codex-gemma-dda1882f352a

Codex and Gemma teacher scores by category

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Teacher spread

0.253 · how far apart the two teachers sit on this one work

Validation status

score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

Several studies have confirmed the α-synuclein real-time quaking-induced conversion (RT-QuIC) 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 α-synuclein RT-QuIC quantitative parameters in regard to disease progression, stratification and conversion in synucleinopathies. We performed α-synuclein 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. α-Synuclein 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. Unified Parkinson's Disease Rating Scale 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 Unified Multiple System Atrophy Rating Scale). 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 at 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 α-synuclein RT-QuIC adds value in diagnosing Parkinson's disease and may provide a way to distinguish variations within Parkinson's disease phenotype. However, the quantitative parameters 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 α-synuclein RT-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 α-synuclein RT-QuIC signature and the progression from prodromal to different synucleinopathies.

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The record

Venue

Brain

Topic

Parkinson's Disease Mechanisms and Treatments

Field

Medicine

Canadian institutions

McGill UniversityMontreal General HospitalUniversité du Québec à MontréalCanadian Sleep & Circadian NetworkUniversité de MontréalCentre Intégré Universitaire de Santé et de Services Sociaux du Centre-Sud-de-l'Île-de-MontréalHôpital du Sacré-Cœur de Montréal

Funders

NIHR Oxford Biomedical Research CentreCanadian Institutes of Health ResearchOtsuka Pharmaceutical Development and CommercializationIdorsia PharmaceuticalsDeutsche Parkinson VereinigungH. Lundbeck A/SJazz PharmaceuticalsParkinson's UKEisaiServierParkinson's FoundationDeutsche ForschungsgemeinschaftEngineering and Physical Sciences Research CouncilUK Research and InnovationNational Institute for Health and Care ResearchTeva Pharmaceutical IndustriesMedical Research CouncilBiogen

Keywords

SynucleinopathiesAtrophyParkinson's diseaseREM sleep behavior disorderDementia with Lewy bodiesPathologyDiseaseMedicineInternal medicineAlpha-synucleinDementia

Has abstract in OpenAlex

yes

API

/api/v1/works/W4200520313