Comparison of ELISA- and SIMOA-based quantification of plasma Aβ 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 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 ).

Authors

Steffi De Meyer; Jolien Schaeverbeke; Inge M.W. Verberk; Benjamin Gille; Maxim De Schaepdryver; Emma S. Luckett; Silvy Gabel; Rose Bruffaerts; Kimberley Mauroo; Elisabeth H. Thijssen; Erik Stoops; Hugo Vanderstichele; Charlotte E. Teunissen; Rik Vandenberghe; Koen Poesen

Published

Dec 1, 2020

Journal or venue

Alzheimer s Research & Therapy

DOI

10.1186/s13195-020-00728-w

Paper type

journal article

Source

Openalex