Dataset Information

Cerebrospinal fluid α-synuclein predicts neurodegeneration and clinical progression in non-demented elders.

ABSTRACT:

Background

Accumulating reports have suggested that α-synuclein is involved in the pathogenesis of Alzheimer's disease (AD). As the cerebrospinal fluid (CSF) α-synuclein has been suggested as a potential biomarker of AD, this study was set out to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented elders.

Methods

The associations between CSF α-synuclein and other AD biomarkers were investigated at baseline in non-demented Chinese elders. The predictive values of CSF α-synuclein for longitudinal neuroimaging change and the conversion risk of non-demented elders were assessed using linear mixed effects models and multivariate Cox proportional hazard models, respectively, in the Alzheimer's disease Neuroimaging Initiative (ADNI) database.

Results

The CSF α-synuclein levels correlated with AD-specific biomarkers, CSF total tau and phosphorylated tau levels, in 651 Chinese Han participants (training set). These positive correlations were replicated in the ADNI database (validation set). Using a longitudinal cohort from ADNI, the CSF α-synuclein concentrations were found to increase with disease severity. The CSF α-synuclein had high diagnostic accuracy for AD based on the "ATN" (amyloid, tau, neurodegeneration) system (A + T+ versus A - T - control) (area under the receiver operating characteristic curve, 0.84). Moreover, CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia.

Conclusions

CSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in non-demented elders. This finding indicates that CSF α-synuclein is a potentially useful early biomarker for AD.

SUBMITTER: Li JQ

PROVIDER: S-EPMC7685645 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Cerebrospinal fluid α-synuclein predicts neurodegeneration and clinical progression in non-demented elders.

Li Jie-Qiong JQ Bi Yan-Lin YL Shen Xue-Ning XN Wang Hui-Fu HF Xu Wei W Tan Chen-Chen CC Dong Qiang Q Wang Yan-Jiang YJ Tan Lan L Yu Jin-Tai JT

Translational neurodegeneration 20201123 1

<h4>Background</h4>Accumulating reports have suggested that α-synuclein is involved in the pathogenesis of Alzheimer's disease (AD). As the cerebrospinal fluid (CSF) α-synuclein has been suggested as a potential biomarker of AD, this study was set out to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in non-demented elders.<h4>Methods</h4>The associations between CSF α-synuclein and other AD biomarkers were investi ...[more]

PMID: 33228804

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Project description: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.

Dataset Information

Cerebrospinal fluid α-synuclein predicts neurodegeneration and clinical progression in non-demented elders.

Background

Methods

Results

Conclusions

Publications

Cerebrospinal fluid α-synuclein predicts neurodegeneration and clinical progression in non-demented elders.

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