Performance assessment of novel chemiluminescence immunoassays for the detection of specific biomarkers for Alzheimer’s disease

Abstract Background To support diagnosis of Alzheimer’s disease (AD), concentrations of Aβ 1‐42 , tTau and pTau(181) and the Aβ 1‐42 /Aβ 1‐40 ratio are determined in cerebrospinal fluid (CSF). To increase standardization and comparability between diagnostic laboratories, certified reference material (CRM) is used to evaluate the trueness of novel assays. Due to lack of CRMs for tTau, pTau(181), and Aβ 1‐40 , comparability may be assessed by comparing assays from different manufacturers. This study compares the performance of novel chemiluminescence immunoassays (ChLIAs) developed by EUROIMMUN with established chemiluminescence assays. Method Biomarker concentrations were determined in 110 CSF samples (patients without known diagnosis; mean age 57.2 years, range 11–94 years; 49 female, 60 male, 1 unknown) using the Beta‐Amyloid (1‐42), Beta‐Amyloid (1‐40), Total‐Tau and pTau(181) ChLIAs (all EUROIMMUN) and the corresponding Lumipulse G assays (Fujirebio). The assays were performed according to the manufacturers’ instructions on the fully automated random‐access devices IDS‐i10 (Immunodiagnostic Systems) and LUMIPULSE G 600II analyzer (Fujirebio), respectively. Agreement of results obtained with the two chemiluminescence systems was calculated. Result Overall agreement ranged from 89.0% to 97.3%. Agreement for the determination of normal biomarker concentrations was 93.4%–100% and 57.7%–94% for abnormal concentrations. The level of agreement was highest for Aβ 1‐42 determination. Pearson’s regression coefficient revealed high correlation of results (R=0.82 to R=0.99 for Aβ 1‐42 determination). While concentrations determined using EUROIMMUN assays were generally higher, numerical differences had minor influence on the diagnostic evaluation. Conclusion Using the EUROIMMUN ChLIAs, AD‐specific biomarkers can be measured with high precision and stability on fully automated random‐access devices. The highest level of agreement and correlation was found for Aβ 1‐42 determination as assays are aligned to the respective CRMs. This indicates the need to introduce CRMs for standardization of tTau, pTau(181), and Aβ 1‐40 assays.