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Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis
BACKGROUND: Blood-based amyloid biomarkers may provide a non-invasive, cost-effective and scalable manner for detecting cerebral amyloidosis in early disease stages. METHODS: In this prospective cross-sectional study, we quantified plasma Aβ(1–42)/Aβ(1–40) ratios with both routinely available ELISAs...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719262/ https://www.ncbi.nlm.nih.gov/pubmed/33278904 http://dx.doi.org/10.1186/s13195-020-00728-w |
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author | De Meyer, Steffi Schaeverbeke, Jolien M. Verberk, Inge M. W. Gille, Benjamin De Schaepdryver, Maxim Luckett, Emma S. Gabel, Silvy Bruffaerts, Rose Mauroo, Kimberley Thijssen, Elisabeth H. Stoops, Erik Vanderstichele, Hugo M. Teunissen, Charlotte E. Vandenberghe, Rik Poesen, Koen |
author_facet | De Meyer, Steffi Schaeverbeke, Jolien M. Verberk, Inge M. W. Gille, Benjamin De Schaepdryver, Maxim Luckett, Emma S. Gabel, Silvy Bruffaerts, Rose Mauroo, Kimberley Thijssen, Elisabeth H. Stoops, Erik Vanderstichele, Hugo M. Teunissen, Charlotte E. Vandenberghe, Rik Poesen, Koen |
author_sort | De Meyer, Steffi |
collection | PubMed |
description | BACKGROUND: Blood-based amyloid biomarkers may provide a non-invasive, cost-effective and scalable manner for detecting cerebral amyloidosis in early disease stages. METHODS: In this prospective cross-sectional study, we quantified plasma Aβ(1–42)/Aβ(1–40) ratios with both routinely available ELISAs and novel SIMOA Amyblood assays, and provided a head-to-head comparison of their performances to detect cerebral amyloidosis in a nondemented elderly cohort (n = 199). Participants were stratified according to amyloid-PET status, and the performance of plasma Aβ(1–42)/Aβ(1–40) to detect cerebral amyloidosis was assessed using receiver operating characteristic analysis. We additionally investigated the correlations of plasma Aβ ratios with amyloid-PET and CSF Alzheimer’s disease biomarkers, as well as platform agreement using Passing-Bablok regression and Bland-Altman analysis for both Aβ isoforms. RESULTS: ELISA and SIMOA plasma Aβ(1–42)/Aβ(1–40) detected cerebral amyloidosis with identical accuracy (ELISA: area under curve (AUC) 0.78, 95% CI 0.72–0.84; SIMOA: AUC 0.79, 95% CI 0.73–0.85), and both increased the performance of a basic demographic model including only age and APOE-ε4 genotype (p ≤ 0.02). ELISA and SIMOA had positive predictive values of respectively 41% and 36% in cognitively normal elderly and negative predictive values all exceeding 88%. Plasma Aβ(1–42)/Aβ(1–40) correlated similarly with amyloid-PET for both platforms (Spearman ρ = − 0.32, p < 0.0001), yet correlations with CSF Aβ(1–42)/t-tau were stronger for ELISA (ρ = 0.41, p = 0.002) than for SIMOA (ρ = 0.29, p = 0.03). Plasma Aβ levels demonstrated poor agreement between ELISA and SIMOA with concentrations of both Aβ(1–42) and Aβ(1–40) measured by SIMOA consistently underestimating those measured by ELISA. CONCLUSIONS: ELISA and SIMOA demonstrated equivalent performances in detecting cerebral amyloidosis through plasma Aβ(1–42)/Aβ(1–40), both with high negative predictive values, making them equally suitable non-invasive prescreening tools for clinical trials by reducing the number of necessary PET scans for clinical trial recruitment. TRIAL REGISTRATION: EudraCT 2009-014475-45 (registered on 23 Sept 2009) and EudraCT 2013-004671-12 (registered on 20 May 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004671-12/BE). |
format | Online Article Text |
id | pubmed-7719262 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-77192622020-12-07 Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis De Meyer, Steffi Schaeverbeke, Jolien M. Verberk, Inge M. W. Gille, Benjamin De Schaepdryver, Maxim Luckett, Emma S. Gabel, Silvy Bruffaerts, Rose Mauroo, Kimberley Thijssen, Elisabeth H. Stoops, Erik Vanderstichele, Hugo M. Teunissen, Charlotte E. Vandenberghe, Rik Poesen, Koen Alzheimers Res Ther Research BACKGROUND: Blood-based amyloid biomarkers may provide a non-invasive, cost-effective and scalable manner for detecting cerebral amyloidosis in early disease stages. METHODS: In this prospective cross-sectional study, we quantified plasma Aβ(1–42)/Aβ(1–40) ratios with both routinely available ELISAs and novel SIMOA Amyblood assays, and provided a head-to-head comparison of their performances to detect cerebral amyloidosis in a nondemented elderly cohort (n = 199). Participants were stratified according to amyloid-PET status, and the performance of plasma Aβ(1–42)/Aβ(1–40) to detect cerebral amyloidosis was assessed using receiver operating characteristic analysis. We additionally investigated the correlations of plasma Aβ ratios with amyloid-PET and CSF Alzheimer’s disease biomarkers, as well as platform agreement using Passing-Bablok regression and Bland-Altman analysis for both Aβ isoforms. RESULTS: ELISA and SIMOA plasma Aβ(1–42)/Aβ(1–40) detected cerebral amyloidosis with identical accuracy (ELISA: area under curve (AUC) 0.78, 95% CI 0.72–0.84; SIMOA: AUC 0.79, 95% CI 0.73–0.85), and both increased the performance of a basic demographic model including only age and APOE-ε4 genotype (p ≤ 0.02). ELISA and SIMOA had positive predictive values of respectively 41% and 36% in cognitively normal elderly and negative predictive values all exceeding 88%. Plasma Aβ(1–42)/Aβ(1–40) correlated similarly with amyloid-PET for both platforms (Spearman ρ = − 0.32, p < 0.0001), yet correlations with CSF Aβ(1–42)/t-tau were stronger for ELISA (ρ = 0.41, p = 0.002) than for SIMOA (ρ = 0.29, p = 0.03). Plasma Aβ levels demonstrated poor agreement between ELISA and SIMOA with concentrations of both Aβ(1–42) and Aβ(1–40) measured by SIMOA consistently underestimating those measured by ELISA. CONCLUSIONS: ELISA and SIMOA demonstrated equivalent performances in detecting cerebral amyloidosis through plasma Aβ(1–42)/Aβ(1–40), both with high negative predictive values, making them equally suitable non-invasive prescreening tools for clinical trials by reducing the number of necessary PET scans for clinical trial recruitment. TRIAL REGISTRATION: EudraCT 2009-014475-45 (registered on 23 Sept 2009) and EudraCT 2013-004671-12 (registered on 20 May 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004671-12/BE). BioMed Central 2020-12-05 /pmc/articles/PMC7719262/ /pubmed/33278904 http://dx.doi.org/10.1186/s13195-020-00728-w Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research De Meyer, Steffi Schaeverbeke, Jolien M. Verberk, Inge M. W. Gille, Benjamin De Schaepdryver, Maxim Luckett, Emma S. Gabel, Silvy Bruffaerts, Rose Mauroo, Kimberley Thijssen, Elisabeth H. Stoops, Erik Vanderstichele, Hugo M. Teunissen, Charlotte E. Vandenberghe, Rik Poesen, Koen Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis |
title | Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis |
title_full | Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis |
title_fullStr | Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis |
title_full_unstemmed | Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis |
title_short | Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis |
title_sort | comparison of elisa- and simoa-based quantification of plasma aβ ratios for early detection of cerebral amyloidosis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719262/ https://www.ncbi.nlm.nih.gov/pubmed/33278904 http://dx.doi.org/10.1186/s13195-020-00728-w |
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