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. 2016 Sep 7;11(1):65.
doi: 10.1186/s13024-016-0130-3.

No diurnal variation of classical and candidate biomarkers of Alzheimer's disease in CSF

Claudia Cicognola  1   2 , Davide Chiasserini  3 , Paolo Eusebi  3 , Ulf Andreasson  1   2 , Hugo Vanderstichele  4 , Henrik Zetterberg  1   2   5 , Lucilla Parnetti  6 , Kaj Blennow  1   2
Affiliations

No diurnal variation of classical and candidate biomarkers of Alzheimer's disease in CSF

Claudia Cicognola et al. Mol Neurodegener. .

Abstract

Background: Cerebrospinal fluid (CSF) biomarkers have gained increasing importance in the diagnostic work-up of Alzheimer's disease (AD). The core CSF biomarkers related to AD pathology (Aβ42, t-tau and p-tau) are currently used in CSF diagnostics, while candidate markers of amyloid metabolism (Aβ38, Aβ40, sAPPα, sAPPβ), synaptic loss (neurogranin), neuroinflammation (YKL-40), neuronal damage (VILIP-1) and genetic risk (apolipoprotein E) are undergoing evaluation. Diurnal fluctuation in the concentration of CSF biomarkers has been reported and may represent a preanalytical confounding factor in the laboratory diagnosis of AD. The aim of the present study was to investigate the diurnal variability of classical and candidate CSF biomarkers in a cohort of neurosurgical patients carrying a CSF drainage.

Method: Samples were collected from a cohort of 13 neurosurgical patients from either ventricular (n = 6) or lumbar (n = 7) CSF drainage at six time points during the day, 1-7 days following the neurosurgical intervention. Concentrations of the core biomarkers were determined by immunoassays.

Results: Although absolute values largely varied among subjects, none of the biomarkers showed significant diurnal variation. Site of drainage (lumbar vs. ventricular) did not influence this result. The different immunoassays used for tau and Aβ markers provided similar results.

Conclusion: Time of day at CSF collection does not ultimately affect the concentration levels of classical and candidate AD biomarkers. Similar trends were found when using different immunoassays, thus corroborating the consistency of the data.

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Figures

Fig. 1
Fig. 1
Correlation of the levels of biomarkers measured with different assays (Euroimmun, MSD, Fujirebio)
Fig. 2
Fig. 2
Concentration levels of the biomarkers across time points (horizontal lines representing the median, box representing the 25th and 75th percentiles, whiskers representing the 5th and 95th percentiles, and outliers represented by dots)
Fig. 3
Fig. 3
Concentration levels of several biomarkers measured with different assays (Euroimmun, MSD, Fujirebio) across time points (horizontal lines representing the median, box representing the 25th and 75th percentiles, whiskers representing the 5th and 95th percentiles)
Fig. 4
Fig. 4
Concentration levels of several biomarkers with different type of drainage (lumbar or ventricular) across time points (horizontal lines representing the median, box representing the 25th and 75th percentiles, whiskers representing the 5th and 95th percentiles). Pictures not showed for non-significant comparisons
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