Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer's disease
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/106802 https://doi.org/10.1186/s13195-019-0550-8 |
Resumo: | Background: Ongoing efforts within the Alzheimer’s disease (AD) field have focused on improving the intra- and inter-laboratory variability for cerebrospinal fluid (CSF) biomarkers. Fully automated assays offer the possibility to eliminate sample manipulation steps and are expected to contribute to this improvement. Recently, fully automated chemiluminescence enzyme immunoassays for the quantification of all four AD biomarkers in CSF became available. The aims of this study were to (i) evaluate the analytical performance of the Lumipulse G β-Amyloid 1-42 (restandardized to Certified Reference Materials), β-Amyloid 1-40, total Tau, and pTau 181 assays on the fully automated LUMIPULSE G600II; (ii) compare CSF biomarker results of the Lumipulse G assays with the established manual ELISA assays (INNOTEST®) from the same company (Fujirebio); and (iii) establish cut-off values and the clinical performance of the Lumipulse G assays for AD diagnosis. Methods: Intra- and inter-assay variation was assessed in CSF samples with low, medium, and high concentrations of each parameter. Method comparison and clinical evaluation were performed on 40 neurological controls (NC) and 80 patients with a diagnosis of probable AD supported by a follow-up ≥ 3 years and/or positive amyloid PET imaging. A small validation cohort of 10 NC and 20 AD patients was also included to validate the cut-off values obtained on the training cohort. Results: The maximal observed intra-assay and inter-assay coefficients of variation (CVs) were 3.25% and 5.50%, respectively. Method comparisons revealed correlation coefficients ranging from 0.89 (for Aβ40) to 0.98 (for t-Tau), with those for Aβ42 (0.93) and p-Tau (0.94) in-between. ROC curve analysis showed area under the curve values consistently above 0.85 for individual biomarkers other than Aβ40, and with the Aβ42/40, Aβ42/t-Tau, and Aβ42/ p-Tau ratios outperforming Aβ42. Validation of the cut-off values in the independent cohort showed a sensitivity ranging from 75 to 95% and a specificity of 100%. The overall percentage of agreement between Lumipulse and INNOTEST was very high (> 87.5%). Conclusions: The Lumipulse G assays show a very good analytical performance that makes them well-suited for CSF clinical routine measurements. The good clinical concordance between the Lumipulse G and INNOTEST assays facilitates the implementation of the new method in routine practice. |
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Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer's diseaseAlzheimer’s disease,Cerebrospinal fluid,Biomarkers,Chemiluminescent enzyme-automated immunoassayAgedAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersEnzyme-Linked Immunosorbent AssayFemaleHumansMaleMiddle AgedPeptide Fragmentstau ProteinsBackground: Ongoing efforts within the Alzheimer’s disease (AD) field have focused on improving the intra- and inter-laboratory variability for cerebrospinal fluid (CSF) biomarkers. Fully automated assays offer the possibility to eliminate sample manipulation steps and are expected to contribute to this improvement. Recently, fully automated chemiluminescence enzyme immunoassays for the quantification of all four AD biomarkers in CSF became available. The aims of this study were to (i) evaluate the analytical performance of the Lumipulse G β-Amyloid 1-42 (restandardized to Certified Reference Materials), β-Amyloid 1-40, total Tau, and pTau 181 assays on the fully automated LUMIPULSE G600II; (ii) compare CSF biomarker results of the Lumipulse G assays with the established manual ELISA assays (INNOTEST®) from the same company (Fujirebio); and (iii) establish cut-off values and the clinical performance of the Lumipulse G assays for AD diagnosis. Methods: Intra- and inter-assay variation was assessed in CSF samples with low, medium, and high concentrations of each parameter. Method comparison and clinical evaluation were performed on 40 neurological controls (NC) and 80 patients with a diagnosis of probable AD supported by a follow-up ≥ 3 years and/or positive amyloid PET imaging. A small validation cohort of 10 NC and 20 AD patients was also included to validate the cut-off values obtained on the training cohort. Results: The maximal observed intra-assay and inter-assay coefficients of variation (CVs) were 3.25% and 5.50%, respectively. Method comparisons revealed correlation coefficients ranging from 0.89 (for Aβ40) to 0.98 (for t-Tau), with those for Aβ42 (0.93) and p-Tau (0.94) in-between. ROC curve analysis showed area under the curve values consistently above 0.85 for individual biomarkers other than Aβ40, and with the Aβ42/40, Aβ42/t-Tau, and Aβ42/ p-Tau ratios outperforming Aβ42. Validation of the cut-off values in the independent cohort showed a sensitivity ranging from 75 to 95% and a specificity of 100%. The overall percentage of agreement between Lumipulse and INNOTEST was very high (> 87.5%). Conclusions: The Lumipulse G assays show a very good analytical performance that makes them well-suited for CSF clinical routine measurements. The good clinical concordance between the Lumipulse G and INNOTEST assays facilitates the implementation of the new method in routine practice.Springer Nature2019-11-23info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/106802http://hdl.handle.net/10316/106802https://doi.org/10.1186/s13195-019-0550-8eng1758-9193Leitão, Maria JoãoSpínola, Anuschka da SilvaSantana, IsabelOlmedo, VeronicaNadal, AliciaLe Bastard, NathalieBaldeiras, Inêsinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-04-24T08:42:11Zoai:estudogeral.uc.pt:10316/106802Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:12.132143Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer's disease |
title |
Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer's disease |
spellingShingle |
Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer's disease Leitão, Maria João Alzheimer’s disease, Cerebrospinal fluid, Biomarkers, Chemiluminescent enzyme-automated immunoassay Aged Alzheimer Disease Amyloid beta-Peptides Biomarkers Enzyme-Linked Immunosorbent Assay Female Humans Male Middle Aged Peptide Fragments tau Proteins |
title_short |
Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer's disease |
title_full |
Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer's disease |
title_fullStr |
Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer's disease |
title_full_unstemmed |
Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer's disease |
title_sort |
Clinical validation of the Lumipulse G cerebrospinal fluid assays for routine diagnosis of Alzheimer's disease |
author |
Leitão, Maria João |
author_facet |
Leitão, Maria João Spínola, Anuschka da Silva Santana, Isabel Olmedo, Veronica Nadal, Alicia Le Bastard, Nathalie Baldeiras, Inês |
author_role |
author |
author2 |
Spínola, Anuschka da Silva Santana, Isabel Olmedo, Veronica Nadal, Alicia Le Bastard, Nathalie Baldeiras, Inês |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Leitão, Maria João Spínola, Anuschka da Silva Santana, Isabel Olmedo, Veronica Nadal, Alicia Le Bastard, Nathalie Baldeiras, Inês |
dc.subject.por.fl_str_mv |
Alzheimer’s disease, Cerebrospinal fluid, Biomarkers, Chemiluminescent enzyme-automated immunoassay Aged Alzheimer Disease Amyloid beta-Peptides Biomarkers Enzyme-Linked Immunosorbent Assay Female Humans Male Middle Aged Peptide Fragments tau Proteins |
topic |
Alzheimer’s disease, Cerebrospinal fluid, Biomarkers, Chemiluminescent enzyme-automated immunoassay Aged Alzheimer Disease Amyloid beta-Peptides Biomarkers Enzyme-Linked Immunosorbent Assay Female Humans Male Middle Aged Peptide Fragments tau Proteins |
description |
Background: Ongoing efforts within the Alzheimer’s disease (AD) field have focused on improving the intra- and inter-laboratory variability for cerebrospinal fluid (CSF) biomarkers. Fully automated assays offer the possibility to eliminate sample manipulation steps and are expected to contribute to this improvement. Recently, fully automated chemiluminescence enzyme immunoassays for the quantification of all four AD biomarkers in CSF became available. The aims of this study were to (i) evaluate the analytical performance of the Lumipulse G β-Amyloid 1-42 (restandardized to Certified Reference Materials), β-Amyloid 1-40, total Tau, and pTau 181 assays on the fully automated LUMIPULSE G600II; (ii) compare CSF biomarker results of the Lumipulse G assays with the established manual ELISA assays (INNOTEST®) from the same company (Fujirebio); and (iii) establish cut-off values and the clinical performance of the Lumipulse G assays for AD diagnosis. Methods: Intra- and inter-assay variation was assessed in CSF samples with low, medium, and high concentrations of each parameter. Method comparison and clinical evaluation were performed on 40 neurological controls (NC) and 80 patients with a diagnosis of probable AD supported by a follow-up ≥ 3 years and/or positive amyloid PET imaging. A small validation cohort of 10 NC and 20 AD patients was also included to validate the cut-off values obtained on the training cohort. Results: The maximal observed intra-assay and inter-assay coefficients of variation (CVs) were 3.25% and 5.50%, respectively. Method comparisons revealed correlation coefficients ranging from 0.89 (for Aβ40) to 0.98 (for t-Tau), with those for Aβ42 (0.93) and p-Tau (0.94) in-between. ROC curve analysis showed area under the curve values consistently above 0.85 for individual biomarkers other than Aβ40, and with the Aβ42/40, Aβ42/t-Tau, and Aβ42/ p-Tau ratios outperforming Aβ42. Validation of the cut-off values in the independent cohort showed a sensitivity ranging from 75 to 95% and a specificity of 100%. The overall percentage of agreement between Lumipulse and INNOTEST was very high (> 87.5%). Conclusions: The Lumipulse G assays show a very good analytical performance that makes them well-suited for CSF clinical routine measurements. The good clinical concordance between the Lumipulse G and INNOTEST assays facilitates the implementation of the new method in routine practice. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-11-23 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/106802 http://hdl.handle.net/10316/106802 https://doi.org/10.1186/s13195-019-0550-8 |
url |
http://hdl.handle.net/10316/106802 https://doi.org/10.1186/s13195-019-0550-8 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1758-9193 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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