TY - JOUR
T1 - Interlaboratory proficiency processing scheme in CSF aliquoting
T2 - Implementation and assessment based on biomarkers of Alzheimer's disease
AU - Lewczuk, Piotr
AU - Gaignaux, Amélie
AU - Kofanova, Olga
AU - Ermann, Natalia
AU - Betsou, Fay
AU - Brandner, Sebastian
AU - Mroczko, Barbara
AU - Blennow, Kaj
AU - Strapagiel, Dominik
AU - Paciotti, Silvia
AU - Vogelgsang, Jonathan
AU - Roehrl, Michael H.
AU - Mendoza, Sandra
AU - Kornhuber, Johannes
AU - Teunissen, Charlotte
N1 - Funding Information:
The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in-kind contribution. This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. DS and participation in CSF proficiency testing was supported by the Polish Ministry of Science and Higher Education grant DIR/WK/2017/01. CT received grants from the European Commission, the Dutch Research Council (ZonMW), Association of Frontotemporal Dementia/Alzheimer’s Drug Discovery Foundation, and Alzheimer Netherlands.
Funding Information:
PL received consultation and/or lecture honoraria from IBL International, Fujirebio Europe, AJ Roboscreen, and Roche. CT functioned in advisory boards of Fujirebio and Roche, received nonfinancial support in the form of research consumables from ADxNeurosciences and Euroimmun, and performed contract research or received grants from Probiodrug, Janssen Prevention Ca enter, Boehringer, Brainsonline, AxonNeurosciences, EIP farma, and Roche.
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/8/28
Y1 - 2018/8/28
N2 - Background: In this study, we tested to which extent possible between-center differences in standardized operating procedures (SOPs) for biobanking of cerebrospinal fluid (CSF) samples influence the homogeneity of the resulting aliquots and, consequently, the concentrations of the centrally analyzed selected Alzheimer's disease biomarkers. Methods: Proficiency processing samples (PPSs), prepared by pooling of four individual CSF samples, were sent to 10 participating centers, which were asked to perform aliquoting of the PPSs into two secondary aliquots (SAs) under their local SOPs. The resulting SAs were shipped to the central laboratory, where the concentrations of amyloid beta (Aβ) 1-42, pTau181, and albumin were measured in one run with validated routine analytical methods. Total variability of the concentrations, and its within-center and between-center components, were analyzed with hierarchical regression models. Results: We observed neglectable variability in the concentrations of pTau181 and albumin across the centers and the aliquots. In contrast, the variability of the Aβ1-42 concentrations was much larger (overall coefficient of variation 31%), with 28% of the between-laboratory component and 10% of the within-laboratory (i.e., between-aliquot) component. We identified duration of the preparation of the aliquots and the centrifugation force as two potential confounders influencing within-center variability and biomarker concentrations, respectively. Conclusions: Proficiency processing schemes provide objective evidence for the most critical preanalytical variables. Standardization of these variables may significantly enhance the quality of the collected biospecimens. Studies utilizing retrospective samples collected under different local SOPs need to consider such differences in the statistical evaluations of the data.
AB - Background: In this study, we tested to which extent possible between-center differences in standardized operating procedures (SOPs) for biobanking of cerebrospinal fluid (CSF) samples influence the homogeneity of the resulting aliquots and, consequently, the concentrations of the centrally analyzed selected Alzheimer's disease biomarkers. Methods: Proficiency processing samples (PPSs), prepared by pooling of four individual CSF samples, were sent to 10 participating centers, which were asked to perform aliquoting of the PPSs into two secondary aliquots (SAs) under their local SOPs. The resulting SAs were shipped to the central laboratory, where the concentrations of amyloid beta (Aβ) 1-42, pTau181, and albumin were measured in one run with validated routine analytical methods. Total variability of the concentrations, and its within-center and between-center components, were analyzed with hierarchical regression models. Results: We observed neglectable variability in the concentrations of pTau181 and albumin across the centers and the aliquots. In contrast, the variability of the Aβ1-42 concentrations was much larger (overall coefficient of variation 31%), with 28% of the between-laboratory component and 10% of the within-laboratory (i.e., between-aliquot) component. We identified duration of the preparation of the aliquots and the centrifugation force as two potential confounders influencing within-center variability and biomarker concentrations, respectively. Conclusions: Proficiency processing schemes provide objective evidence for the most critical preanalytical variables. Standardization of these variables may significantly enhance the quality of the collected biospecimens. Studies utilizing retrospective samples collected under different local SOPs need to consider such differences in the statistical evaluations of the data.
KW - Alzheimer's disease
KW - Biobanking
KW - Biomarker
KW - Cerebrospinal fluid
KW - Laboratory standardization
UR - http://www.scopus.com/inward/record.url?scp=85052738816&partnerID=8YFLogxK
U2 - 10.1186/s13195-018-0418-3
DO - 10.1186/s13195-018-0418-3
M3 - Article
C2 - 30153863
AN - SCOPUS:85052738816
SN - 1758-9193
VL - 10
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 87
ER -