Title
Diagnostic impact of cerebrospinal fluid biomarker (pre-)analytical variability in Alzheimers diseaseDiagnostic impact of cerebrospinal fluid biomarker (pre-)analytical variability in Alzheimers disease
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
Neurochemistry and behaviour
Faculteit Geneeskunde
Publication type
article
Publication
Subject
Human medicine
Source (journal)
Journal of Alzheimer's disease
Volume/pages
51(2016):1, p. 97-106
ISSN
1387-2877
ISI
000372181900011
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Intra- and inter-laboratory variability of cerebrospinal fluid (CSF) biomarker analyses remains an important issue. We investigated the clinical-diagnostic impact of CSF biomarker concentration shifts in mild cognitive impairment (MCI) and autopsy-confirmed Alzheimers disease (AD) dementia patients. MCI patients (n&#8202;=&#8202;85), autopsy-confirmed AD dementia patients (n&#8202;=&#8202;72), and cognitively healthy controls (n&#8202;=&#8202;100) were included in this prospective, longitudinal study. AD dementia patients were followed up until death, and controls were included from 1992 until 2003. In-house validated cutoff values of biomarkers were applied: Aβ 1-42 <638.5 pg/mL, T-tau>296.5 pg/mL, P-tau181P >56.5 pg/mL. Both increments and decrements (from ± 5% to ± 40% ) were added to the true (=observed) CSF biomarker values, imitating the anticipated differences in biomarker concentrations. Within certain limits, the clinical diagnostic performance of AD CSF biomarkers remains largely unchanged and clinical diagnostic accuracy deviated less than 8.2% from the reference when concentration shifts ranging between 20% and +20% were added to one of the three CSF biomarkers in MCI and autopsy-confirmed AD patients. Notwithstanding the fact that (pre- and post-)analytical parameters can affect the clinical classification, the present exploratory study provides evidence that for a specific context of use, the impact on clinical accuracy of biomarker concentration shifts might be lower than originally expected. In conclusion, induced shifts of ± 20% in only one of the three biomarkers has limited impact on the clinical accuracy of AD CSF biomarkers in MCI and autopsy-confirmed AD patients when using the IWG-2 criteria.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/4fd800/130884.pdf
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