Interlaboratory proficiency processing scheme in CSF aliquoting: Implementation and assessment based on biomarkers of Alzheimer's disease

Piotr Lewczuk, Amélie Gaignaux, Olga Kofanova, Natalia Ermann, Fay Betsou, Sebastian Brandner, Barbara Mroczko, Kaj Blennow, Dominik Strapagiel, Silvia Paciotti, Jonathan Vogelgsang, Michael H. Roehrl, Sandra Mendoza, Johannes Kornhuber, Charlotte Teunissen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Article number87
JournalAlzheimer's Research and Therapy
Volume10
Issue number1
DOIs
Publication statusPublished - 2018

Cite this

Lewczuk, Piotr ; Gaignaux, Amélie ; Kofanova, Olga ; Ermann, Natalia ; Betsou, Fay ; Brandner, Sebastian ; Mroczko, Barbara ; Blennow, Kaj ; Strapagiel, Dominik ; Paciotti, Silvia ; Vogelgsang, Jonathan ; Roehrl, Michael H. ; Mendoza, Sandra ; Kornhuber, Johannes ; Teunissen, Charlotte. / Interlaboratory proficiency processing scheme in CSF aliquoting: Implementation and assessment based on biomarkers of Alzheimer's disease. In: Alzheimer's Research and Therapy. 2018 ; Vol. 10, No. 1.
@article{b359cf73c7874db4807cda16e68bc1b1,
title = "Interlaboratory proficiency processing scheme in CSF aliquoting: Implementation and assessment based on biomarkers of Alzheimer's disease",
abstract = "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.",
author = "Piotr Lewczuk and Am{\'e}lie Gaignaux and Olga Kofanova and Natalia Ermann and Fay Betsou and Sebastian Brandner and Barbara Mroczko and Kaj Blennow and Dominik Strapagiel and Silvia Paciotti and Jonathan Vogelgsang and Roehrl, {Michael H.} and Sandra Mendoza and Johannes Kornhuber and Charlotte Teunissen",
year = "2018",
doi = "10.1186/s13195-018-0418-3",
language = "English",
volume = "10",
journal = "Alzheimer's Research & Therapy",
issn = "1758-9193",
publisher = "BioMed Central",
number = "1",

}

Lewczuk, P, Gaignaux, A, Kofanova, O, Ermann, N, Betsou, F, Brandner, S, Mroczko, B, Blennow, K, Strapagiel, D, Paciotti, S, Vogelgsang, J, Roehrl, MH, Mendoza, S, Kornhuber, J & Teunissen, C 2018, 'Interlaboratory proficiency processing scheme in CSF aliquoting: Implementation and assessment based on biomarkers of Alzheimer's disease' Alzheimer's Research and Therapy, vol. 10, no. 1, 87. https://doi.org/10.1186/s13195-018-0418-3

Interlaboratory proficiency processing scheme in CSF aliquoting: Implementation and assessment based on biomarkers of Alzheimer's disease. / Lewczuk, Piotr; Gaignaux, Amélie; Kofanova, Olga; Ermann, Natalia; Betsou, Fay; Brandner, Sebastian; Mroczko, Barbara; Blennow, Kaj; Strapagiel, Dominik; Paciotti, Silvia; Vogelgsang, Jonathan; Roehrl, Michael H.; Mendoza, Sandra; Kornhuber, Johannes; Teunissen, Charlotte.

In: Alzheimer's Research and Therapy, Vol. 10, No. 1, 87, 2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Interlaboratory proficiency processing scheme in CSF aliquoting: 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

PY - 2018

Y1 - 2018

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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85052738816&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30153863

U2 - 10.1186/s13195-018-0418-3

DO - 10.1186/s13195-018-0418-3

M3 - Article

VL - 10

JO - Alzheimer's Research & Therapy

JF - Alzheimer's Research & Therapy

SN - 1758-9193

IS - 1

M1 - 87

ER -