Variability of CSF Alzheimer's Disease Biomarkers: Implications for Clinical Practice

S.J.B. Vos, P.J. Visser, F. Verhey, P. Aalten, D. Knol, I. Ramakers, P. Scheltens, M.G.M.O. Rikkert, M.M. Verbeek, C.E. Teunissen

    Research output: Contribution to JournalArticleAcademicpeer-review

    Abstract

    Background: Cerebrospinal fluid (CSF) biomarkers are increasingly being used for diagnosis of Alzheimer's disease (AD). Objective: We investigated the influence of CSF intralaboratory and interlaboratory variability on diagnostic CSF-based AD classification of subjects and identified causes of this variation. Methods: We measured CSF amyloid-β (Aβ) 1-42, total tau (t-tau), and phosphorylated tau (p-tau) by INNOTEST enzyme-linked-immunosorbent assays (ELISA) in a memory clinic population (n = 126). Samples were measured twice in a single or two laboratories that served as reference labs for CSF analyses in the Netherlands. Predefined cut-offs were used to classify CSF biomarkers as normal or abnormal/AD pattern. Results: CSF intralaboratory variability was higher for Aβ1-42 than for t-tau and p-tau. Reanalysis led to a change in biomarker classification (normal vs. abnormal) of 26% of the subjects based on Aβ1-42, 10% based on t-tau, and 29% based on p-tau. The changes in absolute biomarker concentrations were paralleled by a similar change in levels of internal control samples between different assay lots. CSF interlaboratory variability was higher for p-tau than for Aβ1-42 and t-tau, and reanalysis led to a change in biomarker classification of 12% of the subjects based on Aβ1-42, 1% based on t-tau, and 22% based on p-tau. Conclusions: Intralaboratory and interlaboratory CSF variability frequently led to change in diagnostic CSF-based AD classification for Aβ1-42 and p-tau. Lot-to-lot variation was a major cause of intralaboratory variability. This will have implications for the use of these biomarkers in clinical practice. © 2014 Vos et al.
    Original languageEnglish
    Article numbere100784
    Pages (from-to)e100784
    JournalPLoS ONE
    Volume9
    Issue number6
    DOIs
    Publication statusPublished - 2014

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