Toward alpha‐synuclein seed amplification assay in clinical practice

Toward alpha‐synuclein seed amplification assay in clinical practice

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 s...

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Main Authors: Mathieu Verdurand, Flora Kaczorowski, Sophie Dautricourt, Virginie Desestret, Maïté Formaglio, Hélène Mollion, Gil Petitnicolas, Ali Afifi, Anthony Fourier, Antoine Garnier‐Crussard, Isabelle Quadrio
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring
Subjects:
alpha‐synuclein (α‐synuclein)
aSyn
biomarker
brain homogenate (BH)
cerebrospinal fluid (CSF)
dementia with Lewy bodies (DLB)
Online Access:https://doi.org/10.1002/dad2.70066
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Summary: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.
ISSN:2352-8729

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