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

Abstract

BackgroundIn 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.MethodsProficiency 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.ResultsWe 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.ConclusionsProficiency 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.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0418-3) contains supplementary material, which is available to authorized users.

Combination of plasma amyloid beta(1-42/1-40) and glial fibrillary acidic protein strongly associates with cerebral amyloid pathology

“…GFAP might have more favorable characteristics for easier and reliable quantification as compared to Abeta (1-42/1-40) , since GFAP concentrations in blood are much higher. Furthermore, Abeta (1-42/1-40) is a sticky and aggregation-prone protein of which the accurate and robust measurement both in plasma and CSF is influenced by pre-analytical sample handling factors [ 52 – 54 ]. Pre-analytical studies for all novel blood-based biomarkers will help further elucidating their diagnostic utility.…”

2020 update on the clinical validity of cerebrospinal fluid amyloid, tau, and phospho-tau as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework

“…Concentrations of CSF AD biomarkers can be affected by operator-influenced preanalytical variables [23,24], including sampling materials and methodology as well as handling and storage procedures [23,[25][26][27][28][29][30][31][32]. The consensus within the field is that together with appropriate use criteria [33], certified reference methods and materials [22], and high precision measurements [34], the standardization of these factors will reduce variability and increase the diagnostic accuracy of these measures; this, in turn, will facilitate widespread use of CSF AD biomarkers in both clinical research and routine clinical practice [27,35].…”

Quality Management System in the BBMRI.pl Consortium: Status Before the Formation of the Polish Biobanking Network

“…It is worth mentioning that in some of the audited units (16.7%) proficiency testing is performed ac-cording to a quality control plan, for example, the IBBL (Integrated Biobank of Luxembourg): Proficiency Testing Programme (endorsed by the International Society for Biological and Environmental Repositories). 19 External quality control checks for biobanks are performed by many companies and public institutes. The IBBL offers a variety of tests for cell extraction, cell assays, extraction of proteins, and nucleic acids, whereas other institutions offer proficiency testing for transcriptomics and metabolomics.…”