Real-time quaking-induced conversion assay is accurate for Lewy body diseases: a meta-analysis

Wang, Yashan; Hu, Jiayi; Chen, Xiaofei; Wang, Song; Zhang, Chenyang; Hu, Jun‐Jun; Guo, Dingjie; Liu, Xin

doi:10.1007/s10072-022-06014-x

Cited by 5 publications

(5 citation statements)

References 27 publications

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“…Overall, our meta-analysis showed a pooled sensitivity and specificity of 0.88 (95% CI, 0.82-0.93) and 0.95 (95% CI, 0.92-0.97), respectively, to distinguish synucleinopathies from nonsynucleinopathies. There is one previous meta-analysis 58 assessing the performance of RT-QuIC in the diagnosis of LBDs reporting a pooled sensitivity and specificity of 0.91 and 0.95, respectively, which is similar to the results of our analysis. Extending the previous meta-analysis, 58 we have also included studies using PMCA methodology and our study also differs in further methodological aspects: (1) MSA patients were included in the patient group in our main analysis, as α-synuclein aggregates in the form of oligodendroglial cytoplasmic inclusions represent the histopathological hallmark of the disease 1 ; (2) Non-manifesting carriers of genetic mutations associated with synuclein pathology known to cause PD and patients with MCI-LB were also included as they represent prodromal disease stages, in which diagnostic utility of αSyn-SAAs may be of particular relevance for future clinical trials and clinical practice; (3) For the main analysis of the diagnostic accuracy of αSyn-SAAs in the differential diagnosis of synucleinopathies versus nonsynucleinopathies, we included four more studies 34,36,51,56 using RT-QuIC, and three more studies 13,29,38 using PMCA, while we excluded one study 9 of the former meta-analysis because subjects were from the same longitudinal cohort reported in another study 24 ; (4) We performed several subgroup-analyses focusing on different patient cohorts to generate more profound data on the diagnostic utility of RT-QuIC and PMCA in specific clinical settings.…”

Section: Discussionsupporting

confidence: 89%

“…The results of the present and of the previous meta-analysis 58 demonstrate that αSyn-SAAs represent a highly sensitive method for the diagnosis of synucleinopathies and support their usefulness as a diagnostic biomarker in clinical routine work-up. The pooled specificity for differentiating synucleinopathies with LBs from PSP/CBD was high as well with 0.94 (95% CI, 0.79-0.98), although sample sizes for PSP/CBD were rather small in most of the included studies.…”

Section: Reviewsupporting

confidence: 75%

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α‐Synuclein Seed Amplification Assays in the Diagnosis of Synucleinopathies Using Cerebrospinal Fluid—A Systematic Review and Meta‐Analysis

Grossauer

Hemicker

Krismer

et al. 2023

Movement Disord Clin Pract

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Background Real‐time quaking‐induced conversion (RT‐QuIC) and protein misfolding cyclic amplification (PMCA) have been developed to detect minute amounts of amyloidogenic proteins via amplification techniques and have been used to detect misfolded α‐synuclein (αSyn) aggregates in the cerebrospinal fluid (CSF) and other source materials of patients with Parkinson's Disease and other synucleinopathies. Objectives The aim of this systematic review and meta‐analysis was to evaluate the diagnostic accuracy of αSyn seed amplification assays (αSyn‐SAAs), including RT‐QuIC and PMCA, using CSF as source material to differentiate synucleinopathies from controls. Methods The electronic MEDLINE database PubMed was searched for relevant articles published until June 30, 2022. Study quality assessment was performed using the QUADAS‐2 toolbox. A random effects bivariate model was exploited for data synthesis. Results Our systematic review identified 27 eligible studies according to the predefined inclusion criteria, of which 22 were included in the final analysis. Overall, 1855 patients with synucleinopathies and 1378 non‐synucleinopathies as control subjects were included in the meta‐analysis. The pooled sensitivity and specificity to differentiate synucleinopathies from controls with αSyn‐SAA were 0.88 (95% CI, 0.82–0.93) and 0.95 (95% CI, 0.92–0.97), respectively. Evaluating the diagnostic performance of RT‐QuIC in a subgroup analysis for the detection of patients with multiple system atrophy the pooled sensitivity decreased to 0.30 (95% CI, 0.11–0.59). Conclusions While our study clearly demonstrated a high diagnostic performance of RT‐QuIC and PMCA for differentiating synucleinopathies with Lewy bodies from controls, results for the diagnosis of multiple system atrophy were less robust.

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Section: Discussionsupporting

confidence: 89%

Section: Reviewsupporting

confidence: 75%

α‐Synuclein Seed Amplification Assays in the Diagnosis of Synucleinopathies Using Cerebrospinal Fluid—A Systematic Review and Meta‐Analysis

Grossauer

Hemicker

Krismer

et al. 2023

Movement Disord Clin Pract

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“…Real-time shock-induced conversion (RT-QuIC) and protein misfolding cyclic amplification are both SAA ( Shahnawaz et al, 2020 ; Orrù et al, 2021 ; Mammana et al, 2024 ). A meta-analysis demonstrated its ability to accurately and reliably diagnose Lewy body diseases such as PD ( Wang et al, 2022 ). Studies have shown that α-synuclein-specific analyses performed in cerebrospinal fluid (CSF) can differentiate patients with PD from healthy controls with a high degree of sensitivity and specificity ( Siderowf et al, 2023 ).…”

Section: Pathophysiologymentioning

confidence: 99%

Emerging perspectives on precision therapy for Parkinson’s disease: multidimensional evidence leading to a new breakthrough in personalized medicine

Wang,

Gu,

Yang

et al. 2024

Front. Aging Neurosci.

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PD is a prevalent and progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Genes play a significant role in the onset and progression of the disease. While the complexity and pleiotropy of gene expression networks have posed challenges for gene-targeted therapies, numerous pathways of gene variant expression show promise as therapeutic targets in preclinical studies, with some already in clinical trials. With the recognition of the numerous genes and complex pathways that can influence PD, it may be possible to take a novel approach to choose a treatment for the condition. This approach would be based on the symptoms, genomics, and underlying mechanisms of the disease. We discuss the utilization of emerging genetic and pathological knowledge of PD patients to categorize the disease into subgroups. Our long-term objective is to generate new insights for the therapeutic approach to the disease, aiming to delay and treat it more effectively, and ultimately reduce the burden on individuals and society.

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“…Applied to α-synucleinopathies, an abnormal protein would induce the conversion and aggregation of recombinant α-syn that acts as a substrate (please see Figure 1 for a schematic representation). RT-QuIC has sparked great attention during the last years, leading to the publication of several reviews (Kurapova et al, 2022;Srivastava et al, 2022;Y. Wang et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Alpha synuclein by RT-QuIC in dementia with Lewy Bodies: a systematic review and meta-analysis

PEÑA-BAUTISTA¹,

Kumar

Baquero

et al. 2023

Preprint

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Dementia with Lewy Bodies (DLB) is the second most common cause of neurodegenerative dementia but the field is still lacking a specific biomarker for its core pathology: alpha-synuclein. Real-time quaking induced conversion (RT-QuIC) has recently emerged as a strong candidate of alpha-synuclein biomarker. However, the variability in the technique parameters and the heterogeneity of DLB patients makes complex the reproducibility of the results. We provide an overview of the state-of-the-art research with regard to RT-QuIC in DLB focused on: (1) the capacity of RT-QuIC to discriminate DLB from controls, Parkinson’s disease (PD) and Alzheimer’s disease (AD); (2) the capacity of RT-QuIC to identify prodromal stages of DLB; (3) and the influence of co-pathologies on the RT-QuIC’s performance. We also assessed the influence of different factors on the RT-QuIC’s performance, such as technical conditions (e.g. temperature, pH, shaking-rest cycles), sample type, and clinical diagnosis versus autopsy confirmation. Our meta-analysis shows that RT-QuIC reaches very high diagnostic performance in discriminating DLB from both controls (pooled sensitivity and specificity of 0.94 and 0.96, respectively) and AD (pooled sensitivity and specificity of 0.95 and 0.88), and is promising for prodromal phases of DLB). However, the RT-QuIC’s performance to discriminate DLB from PD is currently low due to low specificity (pooled sensitivity and specificity of 0.94 and 0.11). Further, our analyses showed that the RT-QuIC’s performance is not substantialy influenced by sample type or clinical diagnosis versus autopsy confirmation. Co-pathologies did not seem to influence the RT-QuIC’s performance, but the number of studies is currently limited. We observed technical variability across studies but, for the published articles, we could not find that this variability has a clear effect on the reported results. We conclude that there is currently enough evidence to test alpha-synuclein by RT-QuIC for clinical use. We anticipate that harmonization of protocols across centres and advances in standardization will facilitate the clinical establishment and generalization of alpha-synuclein by RT-QuIC.

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Real-time quaking-induced conversion assay is accurate for Lewy body diseases: a meta-analysis

Cited by 5 publications

References 27 publications

α‐Synuclein Seed Amplification Assays in the Diagnosis of Synucleinopathies Using Cerebrospinal Fluid—A Systematic Review and Meta‐Analysis

α‐Synuclein Seed Amplification Assays in the Diagnosis of Synucleinopathies Using Cerebrospinal Fluid—A Systematic Review and Meta‐Analysis

Emerging perspectives on precision therapy for Parkinson’s disease: multidimensional evidence leading to a new breakthrough in personalized medicine

Alpha synuclein by RT-QuIC in dementia with Lewy Bodies: a systematic review and meta-analysis

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