Assessment of the Concordance and Diagnostic Accuracy Between Elecsys and Lumipulse Fully Automated Platforms and Innotest

Abstract

Manual ELISA assays are the most commonly used methods for quantification of biomarkers; however, they often show inter- and intra-laboratory variability that limits their wide use. Here, we compared the Innotest ELISA method with two fully automated platforms (Lumipulse and Elecsys) to determine whether these new methods can provide effective substitutes for ELISA assays. We included 149 patients with AD (n = 34), MCI (n = 94) and non-AD dementias (n = 21). Aβ42, T-tau, and P-tau were quantified using the ELISA method (Innotest, Fujirebio Europe), CLEIA method on a Lumipulse G600II (Fujirebio Diagnostics), and ECLIA method on a Cobas e 601 (Roche Diagnostics) instrument. We found a high correlation between the three methods, although there were systematic differences between biomarker values measured by each method. Both Lumipulse and Elecsys methods were highly concordant with clinical diagnoses, and the combination of Lumipulse Aβ42 and P-tau had the highest discriminating power (AUC 0.915, 95% CI 0.822–1.000). We also assessed the agreement of AT(N) classification for each method with AD diagnosis. Although differences were not significant, the use of Aβ42/Aβ40 ratio instead of Aβ42 alone in AT(N) classification enhanced the diagnostic accuracy (AUC 0.798, 95% CI 0.649–0.947 vs. AUC 0.778, 95% CI 0.617–0.939). We determined the cut-offs for the Lumipulse and Elecsys assays based on the Aβ42/Aβ40 ratio ± status as a marker of amyloid pathology, and these cut-offs were consistent with those recommended by manufacturers, which had been determined based on visual amyloid PET imaging or diagnostic accuracy. Finally, the biomarker ratios (P-tau/Aβ42 and T-tau/Aβ42) were more consistent with the Aβ42/Aβ40 ratio for both Lumipulse and Elecsys methods, and Elecsys P-tau/Aβ42 had the highest consistency with amyloid pathology (AUC 0.994, 95% CI 0.986–1.000 and OPA 96.4%) at the ≥0.024 cut-off. The Lumipulse and Elecsys cerebrospinal fluid (CSF) AD assays showed high analytical and clinical performances. As both automated platforms were standardized for reference samples, their use is recommended for the measurement of CSF AD biomarkers compared with unstandardized manual methods, such as Innotest ELISA, that have demonstrated a high inter and intra-laboratory variability.

β-Amyloid, Tau, Neurodegeneration Classification and Eligibility for Anti-amyloid Treatment in a Memory Clinic Population

“…Potential outlier values were omitted. Based on previous research 29 , Aβ42 was assumed to have similar distributions for both assay types; for Aβ42/40 and p-tau the assays were treated separately. Our data supported this assumption.…”

Tau positron emission tomography, cerebrospinal fluid and plasma biomarkers of neurodegeneration, and neurocognitive testing: an exploratory study of participants with myotonic dystrophy type 1

“…Analysis of the quality controls provided in the kits including three different levels of concentrations for each biomarker showed CV < 5% (2.3%, 4.8%, 5.0% and 4.0%, respectively). Standard CSF cut-offs provided by the manufacturer for distinguishing AD from other dementia and controls were 56.6 pg/mL for phospho-Tau, 400 pg/mL for total-Tau, 600 pg/mL for Aβ 1-42 and 6.9% for Aβ 1-42/Aβ 1-40 ratio [ 4 ].…”

CSF Alzheimer Disease Biomarkers

“…5-7 In attempt to mitigate these issues, fully automated assays have been developed, which use standardized reference samples that reduce variability within and between laboratories. 8-10 For example, the Lumipulse G CSF assays have demonstrated good analytical performance, 11 which is comparable with manual and other automated immunoassays that have been used in the AD research field. 9,12,13 In addition, Lumipulse and Elecsys methods are highly concordant with clinical diagnoses, with recent work suggesting that the Lumipulse Aβ42 and ptau measures provide the highest discriminating power.…”