Browsing by Author "Verbeek, Marcel M."

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    The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis: A review
    (Elsevier, 2018) Hansson, Oskar; Mikulskis, Alvydas; Fagan, Anne M.; Teunissen, Charlotte; Zetterberg, Henrik; Vanderstichele, Hugo; Molinuevo, Jose Luis; Shaw, Leslie M.; Vandijck, Manu; Verbeek, Marcel M.; Savage, Mary; Mattsson, Niklas; Lewczuk, Piotr; Batrla, Richard; Rutz, Sandra; Dean, Robert A.; Blennow, Kaj; Pathology and Laboratory Medicine, School of Medicine
    Introduction Cerebrospinal fluid (CSF) biomarkers have the potential to improve the diagnostic accuracy of Alzheimer's disease, yet there is a lack of harmonized preanalytical CSF handling protocols. Methods This systematic review summarizes the current literature on the influence of preanalytical variables on CSF biomarker concentration. We evaluated the evidence for three core CSF biomarkers: β-amyloid 42, total tau, and phosphorylated tau. Results The clinically important variables with the largest amount of conflicting data included the temperature at which samples are stored, the time nonfrozen samples can be stored, and possible effects of additives such as detergents, blood contamination, and centrifugation. Conversely, we discovered that there is consensus that tube material has a significant effect. Discussion A unified CSF handling protocol is recommended to reduce preanalytical variability and facilitate comparison of CSF biomarkers across studies and laboratories. In future, experiments should use a gold standard with fresh CSF collected in low binding tubes.
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    An integrated multi-study analysis of intra-subject variability in cerebrospinal fluid amyloid-β concentrations collected by lumbar puncture and indwelling lumbar catheter
    (BioMed Central, 2015-07-29) Lucey, Brendan P.; Gonzales, Celedon; Das, Ujjwas; Li, Jinhe; Siemers, Eric R.; Slemmon, J. Randall; Bateman, Randall J.; Huang, Yafei; Fox, Gerard B.; Claassen, Jurgen A.H.R.; Slats, Diane; Verbeek, Marcel M.; Tong, Gary; Soares, Holly; Savage, Mary J.; Kennedy, Matthew; Forman, Mark; Sjögren, Magnus; Margolin, Richard; Chen, Xia; Farlow, Martin R.; Dean, Robert A.; Waring, Jeffrey F.; Department of Neurology, IU School of Medicine
    INTRODUCTION: Amyloid-β (Aβ) has been investigated as a diagnostic biomarker and therapeutic drug target. Recent studies found that cerebrospinal fluid (CSF) Aβ fluctuates over time, including as a diurnal pattern, and increases in absolute concentration with serial collection. It is currently unknown what effect differences in CSF collection methodology have on Aβ variability. In this study, we sought to determine the effect of different collection methodologies on the stability of CSF Aβ concentrations over time. METHODS: Grouped analysis of CSF Aβ levels from multiple industry and academic groups collected by either lumbar puncture (n=83) or indwelling lumbar catheter (n=178). Participants were either placebo or untreated subjects from clinical drug trials or observational studies. Participants had CSF collected by lumbar puncture or lumbar catheter for quantitation of Aβ concentration by enzyme linked immunosorbent assay. Data from all sponsors was converted to percent of the mean for Aβ40 and Aβ42 for comparison. Repeated measures analysis of variance was performed to assess for factors affecting the linear rise of Aβ concentrations over time. RESULTS: Analysis of studies collecting CSF via lumbar catheter revealed tremendous inter-subject variability of Aβ40 and Aβ42 as well as an Aβ diurnal pattern in all of the sponsors' studies. In contrast, Aβ concentrations from CSF samples collected at two time points by lumbar puncture showed no significant differences. Repeated measures analysis of variance found that only time and draw frequency were significantly associated with the slope of linear rise in Aβ40 and Aβ42 concentrations during the first 6 hours of collection. CONCLUSIONS: Based on our findings, we recommend minimizing the frequency of CSF draws in studies measuring Aβ levels and keeping the frequency standardized between experimental groups. The Aβ diurnal pattern was noted in all sponsors' studies and was not an artifact of study design. Averaging Aβ concentrations at each time point is recommended to minimize the effect of individual variability. Indwelling lumbar catheters are an invaluable research tool for following changes in CSF Aβ over 24-48 hours, but factors affecting Aβ concentration such as linear rise and diurnal variation need to be accounted for in planning study designs.