Diagnostic performance of Elecsys immunoassays for cerebrospinal fluid Alzheimer's disease biomarkers in a nonacademic, multicenter memory clinic cohort: The ABIDE project

Abstract

Introduction: We compared the automated Elecsys and manual Innotest immunoassays for cerebrospinal fluid (CSF) Alzheimer's disease biomarkers in a multicenter diagnostic setting.

Methods: We collected CSF samples from 137 participants in eight local memory clinics. Amyloid β(1-42) (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) were centrally analyzed with Innotest and Elecsys assays. Concordances between methods were assessed.

Results: Biomarker results strongly correlated between assays with Spearman's ρ 0.94 for Aβ42, 0.98 for t-tau, and 0.98 for p-tau. Using Gaussian mixture modeling, cohort-specific cut-points were estimated at 1092 pg/mL for Aβ42, 235 pg/mL for t-tau, and 24 pg/mL for p-tau. We found an excellent concordance of biomarker abnormality between assays of 97% for Aβ42 and 96% for both t-tau and p-tau.

Discussion: The high concordances between Elecsys and Innotest in this nonacademic, multicenter cohort support the use of Elecsys for CSF Alzheimer's disease diagnostics and allow conversion of results between methods.

Keywords: Alzheimer's disease; Biomarkers; Cerebrospinal fluid; Clinical setting; Conversion formula; Elecsys; Gaussian mixture modeling; Immunoassay; Innotest; Method comparison; Multicenter study; Nonacademic cohort.

Fig. 1

Schematic overview of preanalytical deviations during CSF sample collection for biomarker measurement. Please note that one sample could be subject to more than one protocol deviation. Percentages relate to the total sample size. Abbreviations: CSF, cerebrospinal fluid; f/t, freeze/thaw cycle.

Fig. 2

Passing–Bablok regression analyses comparing Innotest and Elecsys results and conversion formulas for Aβ42 (A), t-tau (B), and p-tau (C). For Elecsys Aβ42 values >1700 pg/mL, extrapolated values were used for the analysis (see Supplementary Material). Cut-points with 95% confidence interval for Elecsys (horizontal solid and dotted lines) were determined through Gaussian mixture modeling analyses. Abbreviations: Aβ42, amyloid β(1–42); p-tau, phosphorylated tau; t-tau, total tau.

Fig. 3

Spearman correlation, Passing–Bablok regression analysis, and conversion formulas for Aβ42 results in samples with identical preanalytical protocols (A; n = 78) and samples with differences in preanalytical protocols (B; n = 59). The solid diagonal represents the regression line and the gray area represents the 95% CI. Solid horizontal and vertical lines indicate the biomarker cut-points, and dashed lines indicate 95% CI. Abbreviations: Aβ42, amyloid β(1–42); CI, confidence interval; CSF, cerebrospinal fluid; p-tau, phosphorylated tau; t-tau, total tau.

Fig. 4

Gaussian mixture modeling analysis for Elecsys Aβ42 (A), t-tau (B), and p-tau (C) results. Cut-points (striped lines) with 95% CI (dotted lines) were determined through bootstrapping based on the estimated distributions. Bars indicate the observed data. Abbreviations: Aβ42, amyloid β(1–42); CI, confidence interval; p-tau, phosphorylated tau; t-tau, total tau.