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

Journal Contribution - Journal Article

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 Aβ1-42/Aβ1-40 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 Aβ1-42/Aβ1-40 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 Aβ1-42/Aβ1-40 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 Aβ1-42/Aβ1-40 correlated similarly with amyloid-PET for both platforms (Spearman ρ = - 0.32, p <  0.0001), yet correlations with CSF Aβ1-42/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 Aβ1-42 and Aβ1-40 measured by SIMOA consistently underestimating those measured by ELISA. CONCLUSIONS: ELISA and SIMOA demonstrated equivalent performances in detecting cerebral amyloidosis through plasma Aβ1-42/Aβ1-40, 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 ).
Journal: Alzheimer's Research & Therapy
ISSN: 1758-9193
Issue: 1
Volume: 12
Number of pages: 16
Publication year:2020