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Analytical and clinical performances of the automated Lumipulse cerebrospinal fluid Aβ42 and T-Tau assays for Alzheimer’s disease diagnosis

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Abstract

Background

Cerebrospinal fluid (CSF) biomarkers are increasingly used to diagnose Alzheimer’s disease (AD). However, important methodological and technical remain regarding measurement variability between kit providers and users. We compared the Lumipulse fully automated assays with the manual INNOTEST assays (both from Fujirebio Europe NV, Gent, Belgium) on a clinically representative sample of patients and controls.

Methods

CSF samples of 156 patients were used to quantify Amyloïd Aβ1–42 peptide (Aβ1–42) and Total-Tau (T-Tau) protein by chemiluminescent enzyme-immunoassay (Lumipulse). Patients were divided into several subgroups: Alzheimer (AD = 44), mild-cognitive impairment (MCI = 23), other dementias (OD = 36), non-dementing neurological conditions (ND = 11), and controls (CTRL = 42). Clinical cut-offs were determined by comparing AD and CTRL with ROC curves for the two markers and their related ratio (T-Tau/Aβ1–42). Subgroups of 58 (for phosphorylated-Tau) and 115 samples (for Aβ1–42 and T-Tau) were used to evaluate the concordance of this analyzer with the INNOTEST assays.

Results

Lumipulse and INNOTEST assays showed good concordance for all markers, but systematic bias was observed justifying the need to redefine new clinical cut-offs. To discriminate AD from CTRL subjects, T-Tau/Aβ1–42 ratio was the best biomarker, with a cut-off value of 1.12 (sensitivity 81.8% and specificity 92.9%). Similar clinical performances were observed for the Lumipulse and Innotests assays on the subsample of 115 subjects.

Conclusions

Our results demonstrate that the Lumipulse Aβ1–42 and T-Tau assays show good analytical and clinical performances in the context of patient evaluation referred to a memory clinic. Automated analyzers should be preferred for the measurement of CSF AD biomarkers to reduce inter- and intra-laboratory variability.

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Author notes

  1. Adrian Ivanoiu and Vincent van Pesch have contributed equally to this work as senior authors.

Authors and Affiliations

  1. Department of Laboratory Medicine, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200, Brussels, Belgium

    Jean-Louis Bayart & Vincent van Pesch

  2. Neurochemistry Unit, Institute of Neuroscience, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200, Brussels, Belgium

    Vincent van Pesch

  3. Neurology Department, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Avenue Hippocrate, 10, 1200, Brussels, Belgium

    Bernard Hanseeuw, Adrian Ivanoiu & Vincent van Pesch

Authors
  1. Jean-Louis Bayart
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  2. Bernard Hanseeuw
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  3. Adrian Ivanoiu
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  4. Vincent van Pesch
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Correspondence to Vincent van Pesch.

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The authors declare that they have no conflict of interest related to this work.

Ethical standards

The study protocol was in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration. Residual samples used for diagnostic procedures can be used for retrospective academic studies, without any additional informed consent.

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Bayart, JL., Hanseeuw, B., Ivanoiu, A. et al. Analytical and clinical performances of the automated Lumipulse cerebrospinal fluid Aβ42 and T-Tau assays for Alzheimer’s disease diagnosis. J Neurol 266, 2304–2311 (2019). https://doi.org/10.1007/s00415-019-09418-6

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  • DOI: https://doi.org/10.1007/s00415-019-09418-6

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