Elsevier

Clinical Biochemistry

Volume 72, October 2019, Pages 30-38
Clinical Biochemistry

Elecsys® Total-Tau and Phospho-Tau (181P) CSF assays: Analytical performance of the novel, fully automated immunoassays for quantification of tau proteins in human cerebrospinal fluid

https://doi.org/10.1016/j.clinbiochem.2019.05.005Get rights and content
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Highlights

  • Total- and phospho-tau CSF biomarkers can support Alzheimer's disease diagnosis

  • Elecsys® Total-Tau / Phospho-Tau (181P) CSF assays show good analytical performance

  • Elecsys® CSF and commercially available tau assays demonstrate good correlation

  • Our findings support clinical use of Elecsys® Total-Tau and Phospho-Tau CSF assays

Abstract

Background

Total tau (tTau) and phosphorylated 181P tau (pTau) are supportive diagnostic cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease. Manual CSF tau assays are limited by lot-to-lot and between-laboratory variability and long incubation/turnaround times. Elecsys® Total-Tau CSF and Phospho-Tau (181P) CSF immunoassays were developed for fully automated cobas e analyzers, allowing broader access in clinical practice and trials.

Methods

Analytical performance, reproducibility, method comparisons with commercially available assays, and lot-to-lot and platform comparability (cobas e 601/411) of the Elecsys® CSF assays were assessed. Tau distributions and concentration ranges were evaluated in CSF samples from two clinical cohorts.

Results

Both assays showed high sensitivity (limit of quantitation [LoQ]: 63 pg/mL [tTau]; 4 pg/mL [pTau]) and linearity over the measuring range (80–1300 pg/mL; 8–120 pg/mL), which covered the entire concentration range measured in clinical samples. Lot-to-lot and platform comparability demonstrated good consistency (Pearson's r: 0.998; 1.000). Multicenter evaluation coefficients of variation (CVs): repeatability, < 1.8%; intermediate precision, < 2.8%; between-laboratory variability, < 2.7% (both assays); and total reproducibility, < 6.7% (tTau) and < 4.7% (pTau). Elecsys® CSF assays demonstrated good correlation with commercially available tau assays.

Conclusions

Elecsys® Total-Tau CSF and Phospho-Tau (181P) CSF assays demonstrate good analytical performance with clinically relevant measuring ranges; data support their use in clinical trials and practice.

Keywords

Alzheimer's disease
Biomarkers
CSF
Fully automated immunoassay
Phosphorylated tau
Total tau

Abbreviations

Aβ42
amyloid-β (1–42)
AD
Alzheimer's disease
ADNI
Alzheimer's Disease Neuroimaging Initiative
ANOVA
analysis of variance
CLSI
Clinical and Laboratory Standards Institute
CN
cognitively normal
CSF
cerebrospinal fluid
CV
coefficient of variation
ELISA
enzyme-linked immunosorbent assay
FDA
US Food and Drug Administration
HPLC
high-performance liquid chromatography
Ig
immunoglobulin
LC-MS/MS
liquid chromatography-tandem mass spectrometry
LoB
limit of blank
LoD
limit of detection
LoQ
limit of quantitation
MCI
mild cognitive impairment
MCS
mild cognitive symptoms
NC
normal cognition
NIST
National Institute of Standards and Technology
PET
positron emission tomography
pTau
phosphorylated 181P tau
QC
quality control
SCD
subjective cognitive decline
SD
standard deviation
SMC
significant memory concern
tTau
total tau
UPenn
University of Pennsylvania

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