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IntroductionPrior research identified four neurochemical cerebrospinal fluid (CSF) biomarkers, Aβ1–42, Aβ1–40, tTau, and pTau(181), as core diagnostic markers for Alzheimer's disease (AD). Determination of AD biomarkers using immunoassays can support differential diagnosis of AD vs. several neuropsychiatric disorders, which is important because the respective treatment regimens differ. Results of biomarker determination can be classified according to the Amyloid/Tau/Neurodegeneration (ATN) system into profiles. Less is known about the clinical performance of chemiluminescence immunoassays (ChLIA) measuring specific biomarkers in CSF samples from patients suffering from neuropsychiatric impairments with various underlying causes.MethodsChemiluminescence immunoassays (ChLIAs, EUROIMMUN) were used to determine Beta-Amyloid (1–40), Beta-Amyloid (1–42), Total-Tau, and pTau(181) concentrations in precharacterized cerebrospinal fluid (CSF) samples from 219 AD patients, 74 patients with mild cognitive impairment (MCI), and 220 disease control (DC) patients.Results83.0% of AD patients had ATN profiles consistent with AD, whereas 85.5% of DC patients and 77.0% of MCI patients had profiles inconsistent with AD. AD patients showed significantly lower amyloid ratio Aβ1–42/Aβ1–40 (mean: 0.07) and significantly higher concentrations of tTau (mean: 901.6 pg/ml) and pTau(181) (mean: 129 pg/ml) compared to DC and MCI patients (all p values < 0.0071).DiscussionThe ChLIAs effectively determined specific biomarkers and can support differential diagnostics of AD. Their quality was demonstrated in samples from 513 patients with cognitive impairments, representing a realistic mix of underlying causes for seeking treatment at a memory clinic.

Introduction: Robust immunoassays for quantification of Alzheimer's disease (AD)-specific biomarkers are required for routine diagnostics. We report analytical performance characteristics of four new chemiluminescence immunoassays (ChLIA, EUROIMMUN) running on closed, fully automated random-access instruments for quantification of Aβ1-40, Aβ1-42, tTau, and pTau(181) in human cerebrospinal fluid (CSF). Methods: ChLIAs were validated according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Optimal cut-offs for biomarkers and biomarker ratios were determined using samples from 219 AD patients and 220 patients with AD-related symptoms. For performance comparison, biomarker concentrations were measured in 110 diagnostic leftover samples using the ChLIAs and established Lumipulse G assays (Fujirebio). Results: All ChLIAs met CLSI criteria. Overall agreement between assays was 89.0%–97.3 % with highly correlating results (Pearson's correlation coefficients: 0.82–0.99). Passing-Bablok regression analysis revealed systematic differences. Discussion: EUROIMMUN ChLIAs showed good analytical performances and represent new valuable tools for diagnostics of AD.