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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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring |
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| Online Access: | https://doi.org/10.1002/dad2.70066 |
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| author | Mathieu Verdurand Flora Kaczorowski Sophie Dautricourt Virginie Desestret Maïté Formaglio Hélène Mollion Gil Petitnicolas Ali Afifi Anthony Fourier Antoine Garnier‐Crussard Isabelle Quadrio |
| author_facet | Mathieu Verdurand Flora Kaczorowski Sophie Dautricourt Virginie Desestret Maïté Formaglio Hélène Mollion Gil Petitnicolas Ali Afifi Anthony Fourier Antoine Garnier‐Crussard Isabelle Quadrio |
| author_sort | Mathieu Verdurand |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2aa6dd0d34d0413d8d1c6a4ef04898d5 |
| institution | Kabale University |
| issn | 2352-8729 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring |
| spelling | doaj-art-2aa6dd0d34d0413d8d1c6a4ef04898d52025-08-20T03:42:18ZengWileyAlzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring2352-87292025-01-01171n/an/a10.1002/dad2.70066Toward alpha‐synuclein seed amplification assay in clinical practiceMathieu Verdurand0Flora Kaczorowski1Sophie Dautricourt2Virginie Desestret3Maïté Formaglio4Hélène Mollion5Gil Petitnicolas6Ali Afifi7Anthony Fourier8Antoine Garnier‐Crussard9Isabelle Quadrio10Biochemistry and Molecular Biology DepartmentNeurodegenerative PathologiesLBMMSHospices Civils de LyonLyonFranceBiochemistry and Molecular Biology DepartmentNeurodegenerative PathologiesLBMMSHospices Civils de LyonLyonFranceLyon Memory Resources and Research CenterHospices Civils de LyonLyonFranceLyon Memory Resources and Research CenterHospices Civils de LyonLyonFranceLyon Memory Resources and Research CenterHospices Civils de LyonLyonFranceLyon Memory Resources and Research CenterHospices Civils de LyonLyonFranceToulon Memory ClinicHôpital Sainte MusseToulon‐La Seyne Sur MerFranceMâcon Memory ClinicHôpital de MâconMâconFranceBiochemistry and Molecular Biology DepartmentNeurodegenerative PathologiesLBMMSHospices Civils de LyonLyonFranceLyon Memory Resources and Research CenterHospices Civils de LyonLyonFranceBiochemistry and Molecular Biology DepartmentNeurodegenerative PathologiesLBMMSHospices Civils de LyonLyonFranceAbstract 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.https://doi.org/10.1002/dad2.70066alpha‐synuclein (α‐synuclein)aSynbiomarkerbrain homogenate (BH)cerebrospinal fluid (CSF)dementia with Lewy bodies (DLB) |
| spellingShingle | Mathieu Verdurand Flora Kaczorowski Sophie Dautricourt Virginie Desestret Maïté Formaglio Hélène Mollion Gil Petitnicolas Ali Afifi Anthony Fourier Antoine Garnier‐Crussard Isabelle Quadrio Toward alpha‐synuclein seed amplification assay in clinical practice Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring alpha‐synuclein (α‐synuclein) aSyn biomarker brain homogenate (BH) cerebrospinal fluid (CSF) dementia with Lewy bodies (DLB) |
| title | Toward alpha‐synuclein seed amplification assay in clinical practice |
| title_full | Toward alpha‐synuclein seed amplification assay in clinical practice |
| title_fullStr | Toward alpha‐synuclein seed amplification assay in clinical practice |
| title_full_unstemmed | Toward alpha‐synuclein seed amplification assay in clinical practice |
| title_short | Toward alpha‐synuclein seed amplification assay in clinical practice |
| title_sort | toward alpha synuclein seed amplification assay in clinical practice |
| topic | alpha‐synuclein (α‐synuclein) aSyn biomarker brain homogenate (BH) cerebrospinal fluid (CSF) dementia with Lewy bodies (DLB) |
| url | https://doi.org/10.1002/dad2.70066 |
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