Pre-analytical and analytical factors influencing Alzheimer's disease cerebrospinal fluid biomarker variability

Fourier, Anthony; Portelius, Erik; Zetterberg, Henrik; Blennow, Kaj; Quadrio, Isabelle; Perret‐Liaudet, Armand

doi:10.1016/j.cca.2015.05.024

Cited by 71 publications

(55 citation statements)

References 51 publications

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“…The ranges of the biomarkers were very different from the ones available from the literature on optimal cut-offs for AD biomarkers [37]. This is mostly due to the heterogeneity of the population, different for sex, age and diagnosis at admission (Tables 1 and 2).…”

Section: Discussionmentioning

confidence: 88%

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

Cicognola

Chiasserini

Andréasson

et al. 2016

Mol Neurodegeneration

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BackgroundCerebrospinal 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.MethodSamples 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.ResultsAlthough 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.ConclusionTime 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-016-0130-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 88%

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

Cicognola

Chiasserini

Andréasson

et al. 2016

Mol Neurodegeneration

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“…Surprisingly, although huge efforts have been carried out in the study of preanalytical and analytical conditions affecting biomarker outcomes [28][29][30][31] and consensus guidelines have been reported [12,32], just a few studies have reported the performance of a given set of samples in different laboratories, particularly in the case of aSyn [25,[33][34][35][36]. Furthermore, among these studies, some of them are limited by using low numbers of cases, whereas others did not study the performance of the assays on their diagnostic context.…”

Section: Discussionmentioning

confidence: 99%

Interlaboratory validation of cerebrospinal fluid α‐synuclein quantification in the diagnosis of sporadic Creutzfeldt‐Jakob disease

Kruse

Heslegrave

Gupta

et al. 2018

Alz & Dem Diag Ass & Dis Mo

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Introduction Cerebrospinal fluid α-synuclein level is increased in sporadic Creutzfeldt-Jakob disease cases. However, the clinical value of this biomarker remains to be established. In this study, we have addressed the clinical validation parameters and the interlaboratory reproducibility by using an electrochemiluminescent assay. Methods Cerebrospinal fluid α-synuclein was quantified in a total of 188 sporadic Creutzfeldt-Jakob disease and non–Creutzfeldt-Jakob-disease cases to determine sensitivity and specificity values and lot-to-lot variability. Two round robin tests with 70 additional cases were performed in six independent laboratories. Results A sensitivity of 93% and a specificity of 96% were achieved in discriminating sporadic Creutzfeldt-Jakob disease. No differences were detected between lots. The mean interlaboratory coefficient of variation was 23%, and the intralaboratory coefficient of variations ranged 2.70%–11.39%. Overall, 97% of samples were correctly diagnosed. Discussion The herein validated α-synuclein assay is robust, accurate, and reproducible in identifying Creutzfeldt-Jakob disease cases. Thus, it is ready for implementation in the clinical practice to support the diagnosis of Creutzfeldt-Jakob disease.

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“…different CSF collection and processing procedures, repeated freeze-thaw cycles, prolonged or inaccurate storage of samples) and has been shown for other CSF analytes (for review, see ref. 55). …”

Section: Discussionmentioning

confidence: 99%

Glypican-2 levels in cerebrospinal fluid predict the status of adult hippocampal neurogenesis

Lugert

Kremer

Jagasia

et al. 2017

Sci Rep

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Adult hippocampal neurogenesis is a remarkable form of brain plasticity through which new neurons are generated throughout life. Despite its important roles in cognition and emotion and its modulation in various preclinical disease models, the functional importance of adult hippocampal neurogenesis in human health has not been revealed because of a lack of tools for monitoring adult neurogenesis in vivo. Therefore, we performed an unbiased proteomics screen to identify novel proteins expressed during neuronal differentiation using a human neural stem cell model, and we identified the proteoglycan Glypican-2 (Gpc2) as a putative secreted marker of immature neurons. Exogenous Gpc2 binds to FGF2 and inhibits FGF2-induced neural progenitor cell proliferation. Gpc2 is enriched in neurogenic regions of the adult brain. Its expression is increased by physiological stimuli that increase hippocampal neurogenesis and decreased in transgenic models in which neurogenesis is selectively ablated. Changes in neurogenesis also result in changes in Gpc2 protein level in cerebrospinal fluid (CSF). Gpc2 is detectable in adult human CSF, and first pilot experiments with a longitudinal cohort indicate a decrease over time. Thus, Gpc2 may serve as a potential marker to monitor adult neurogenesis in both animal and human physiology and disease, warranting future studies.

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Pre-analytical and analytical factors influencing Alzheimer's disease cerebrospinal fluid biomarker variability

Cited by 71 publications

References 51 publications

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

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

Interlaboratory validation of cerebrospinal fluid α‐synuclein quantification in the diagnosis of sporadic Creutzfeldt‐Jakob disease

Glypican-2 levels in cerebrospinal fluid predict the status of adult hippocampal neurogenesis

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