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

Journal article
Authors Claudia Cicognola
D. Chiasserini
P. Eusebi
Ulf Andreasson
H. Vanderstichele
Henrik Zetterberg
L. Parnetti
Kaj Blennow
Published in Molecular Neurodegeneration
Volume 11
Pages Article number: 65
ISSN 1750-1326
Publication year 2016
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages Article number: 65
Language en
Keywords amyloid precursor protein, visinin-like protein-1, cerebrospinal-fluid, beta-secretase, cognitive decline, consensus paper, alpha-secretase, a-beta, standardization, neurogranin, Neurosciences & Neurology
Subject categories Clinical Medicine


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 (A beta 42, t-tau and p-tau) are currently used in CSF diagnostics, while candidate markers of amyloid metabolism (A beta 38, A beta 40, sAPP alpha, sAPP beta), 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 A beta 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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