Mathieu Verdurand, Flora Kaczorowski, Sophie Dautricourt, Virginie Desestret, Maïté Formaglio, Hélène Mollion, Gil Petitnicolas, Ali Afifi, Anthony Fourier, Antoine Garnier-Crussard, Isabelle Quadrio
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引用次数: 0
Abstract
Introduction: Seed amplification assays (SAAs) demonstrate remarkable diagnostic performance in alpha-synucleinopathies. However, existing protocols lack accessibility in routine laboratories, mainly due to the requirement for in-house production of recombinant alpha-synuclein (aSyn). This study proposes a cerebrospinal fluid (CSF) aSyn-SAA protocol using solely commercial reagents to facilitate its clinical implementation.
Methods: Routine clinical care CSF samples from 126 patients, comprising 47 with Lewy body diseases (LBD) (41 with dementia with Lewy bodies, six with Parkinson's disease), 37 without alpha-synucleinopathy, and 42 with Alzheimer's disease (AD), underwent assessment for aSyn-SAA activity.
Results: CSF aSyn-SAA showed a sensitivity of 72.3% and a specificity of 100% when distinguishing clinically diagnosed LBD patients from those without alpha-synucleinopathy. In AD patients, 14.3% were tested positive for aSyn.
Discussion: The commercial-only CSF aSyn-SAA protocol exhibited excellent specificity when applied to a real-life cohort, signaling progress toward the accessibility of an aSyn biomarker in clinical settings.
Highlights: Diagnosis of LBD through aSyn-SAA lacks accessibility.This commercial-only aSyn-SAA has satisfactory performance in a real-life cohort.A negative aSyn-SAA does not completely exclude a synucleinopathy.Some technical points must be considered when developing aSyn-SAA.aSyn-SAA must be confined to expert laboratories due to prion-like risk management.
期刊介绍：
Alzheimer''s & Dementia: Diagnosis, Assessment & Disease Monitoring (DADM) is an open access, peer-reviewed, journal from the Alzheimer''s Association® that will publish new research that reports the discovery, development and validation of instruments, technologies, algorithms, and innovative processes. Papers will cover a range of topics interested in the early and accurate detection of individuals with memory complaints and/or among asymptomatic individuals at elevated risk for various forms of memory disorders. The expectation for published papers will be to translate fundamental knowledge about the neurobiology of the disease into practical reports that describe both the conceptual and methodological aspects of the submitted scientific inquiry. Published topics will explore the development of biomarkers, surrogate markers, and conceptual/methodological challenges. Publication priority will be given to papers that 1) describe putative surrogate markers that accurately track disease progression, 2) biomarkers that fulfill international regulatory requirements, 3) reports from large, well-characterized population-based cohorts that comprise the heterogeneity and diversity of asymptomatic individuals and 4) algorithmic development that considers multi-marker arrays (e.g., integrated-omics, genetics, biofluids, imaging, etc.) and advanced computational analytics and technologies.
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