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