Dataset Information

Comparison of ELISA- and SIMOA-based quantification of plasma A? ratios for early detection of cerebral amyloidosis.

ABSTRACT: 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 A?_1-42/A?_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 A?_1-42/A?_1-40 to detect cerebral amyloidosis was assessed using receiver operating characteristic analysis. We additionally investigated the correlations of plasma A? 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 A? isoforms.

Results: ELISA and SIMOA plasma A?_1-42/A?_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-?4 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 A?_1-42/A?_1-40 correlated similarly with amyloid-PET for both platforms (Spearman ??=?-?0.32, p?1-42/t-tau were stronger for ELISA (??=?0.41, p?=?0.002) than for SIMOA (??=?0.29, p?=?0.03). Plasma A? levels demonstrated poor agreement between ELISA and SIMOA with concentrations of both A?_1-42 and A?_1-40 measured by SIMOA consistently underestimating those measured by ELISA.

Conclusions: ELISA and SIMOA demonstrated equivalent performances in detecting cerebral amyloidosis through plasma A?_1-42/A?_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 ).

SUBMITTER: De Meyer S

PROVIDER: S-EPMC7719262 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis.

De Meyer Steffi S Schaeverbeke Jolien M JM Verberk Inge M W IMW Gille Benjamin B De Schaepdryver Maxim M Luckett Emma S ES Gabel Silvy S Bruffaerts Rose R Mauroo Kimberley K Thijssen Elisabeth H EH Stoops Erik E Vanderstichele Hugo M HM Teunissen Charlotte E CE Vandenberghe Rik R Poesen Koen K

Alzheimer's research & therapy 20201205 1

<h4>Background</h4>Blood-based amyloid biomarkers may provide a non-invasive, cost-effective and scalable manner for detecting cerebral amyloidosis in early disease stages.<h4>Methods</h4>In this prospective cross-sectional study, we quantified plasma Aβ<sub>1-42</sub>/Aβ<sub>1-40</sub> 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). ...[more]

PMID: 33278904

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Project description:ObjectivesThe purpose of this study was to determine phenotypes characterizing cardiac involvement in AL amyloidosis by using direct (fluorine-18-labeled florbetapir {[18F]florbetapir} positron emission tomography [PET]/computed tomography) and indirect (echocardiography and cardiac magnetic resonance [CMR]) imaging biomarkers of AL amyloidosis.BackgroundCardiac involvement in systemic light chain amyloidosis (AL) is the main determinant of prognosis and, therefore, guides management. The hypothesis of this study was that myocardial AL deposits and expansion of extracellular volume (ECV) could be identified before increases in N-terminal pro-B-type natriuretic peptide or wall thickness.MethodsA total of 45 subjects were prospectively enrolled in 3 groups: 25 with active AL amyloidosis with cardiac involvement (active-CA), 10 with active AL amyloidosis without cardiac involvement by conventional criteria (active-non-CA), and 10 with AL amyloidosis with cardiac involvement in remission for at least 1 year (remission-CA). All subjects underwent echocardiography, CMR, and [18F]florbetapir PET/CT to evaluate cardiac amyloid burden.ResultsThe active-CA group demonstrated the largest myocardial AL amyloid burden, quantified by [18F]florbetapir retention index (RI) 0.110 (interquartile range [IQR]: 0.078 to 0.139) min-1, and the lowest cardiac function by global longitudinal strain (GLS), median GLS -11% (IQR: -8% to -13%). The remission-CA group had expanded extracellular volume (ECV) and [18F]florbetapir RI of 0.097 (IQR: 0.070 to 0.124 min-1), and abnormal GLS despite hematologic remission for >1 year. The active-non-CA cohort had evidence of cardiac amyloid deposition by advanced imaging metrics in 50% of the subjects; cardiac involvement was identified by late gadolinium enhancement in 20%, elevated ECV in 20%, and elevated [18F]florbetapir RI in 50%.ConclusionsEvidence of cardiac amyloid infiltration was found based on direct and indirect imaging biomarkers in subjects without CA by conventional criteria. The findings from [18F]florbetapir PET imaging provided insight into the preclinical disease process and on the basis of interpretation of expanded ECV on CMR and have important implications for future research and clinical management of AL amyloidosis. (Molecular Imaging of Primary Amyloid Cardiomyopathy [MICA]; NCT02641145).

Dataset Information

Comparison of ELISA- and SIMOA-based quantification of plasma A? ratios for early detection of cerebral amyloidosis.

Publications

Comparison of ELISA- and SIMOA-based quantification of plasma Aβ ratios for early detection of cerebral amyloidosis.

Similar Datasets

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