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Published on: May 30, 2015
α-Synuclein Seed Amplification Assays in the Diagnosis of Synucleinopathies Using Cerebrospinal Fluid-A Systematic
Anna Grossauer1, Greta Hemicker1, Florian Krismer1
1Department of Neurology Medical University of Innsbruck Innsbruck Austria.
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.
