Comparison Of Elisa- And Simoa-Based Quantification Of Plasma A Beta 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 A beta(1-42)/A beta(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 beta(1-42)/A beta(1-40) to detect cerebral amyloidosis was assessed using receiver operating characteristic analysis. We additionally investigated the correlations of plasma A beta 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 beta isoforms.Results: ELISA and SIMOA plasma A beta(1-42)/A beta(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-epsilon 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 beta(1-42)/A beta(1-40) correlated similarly with amyloid-PET for both platforms (Spearman rho = - 0.32, p < 0.0001), yet correlations with CSF A beta(1-42)/t-tau were stronger for ELISA (rho = 0.41, p = 0.002) than for SIMOA (rho = 0.29, p = 0.03). Plasma A beta levels demonstrated poor agreement between ELISA and SIMOA with concentrations of both A beta(1-42) and A beta(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 beta(1-42)/A beta(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.