| 1. |
- Bjerke, Maria, 1977, et al.
(författare)
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Assessing the commutability of reference material formats for the harmonization of amyloid beta measurements.
- 2016
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Ingår i: Clinical chemistry and laboratory medicine : CCLM / FESCC. - : Walter de Gruyter GmbH. - 1437-4331 .- 1434-6621. ; 54:7, s. 1177-91
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cerebrospinal fluid (CSF) amyloid-β (Aβ42) peptide is an important biomarker for Alzheimer's disease (AD). Variability in measured Aβ42 concentrations at different laboratories may be overcome by standardization and establishing traceability to a reference system. Candidate certified reference materials (CRMs) are validated herein for this purpose. METHODS: Commutability of 16 candidate CRM formats was assessed across five CSF Aβ42 immunoassays and one mass spectrometry (MS) method in a set of 48 individual clinical CSF samples. Promising candidate CRM formats (neat CSF and CSF spiked with Aβ42) were identified and subjected to validation across eight (Elecsys, EUROIMMUN, IBL, INNO-BIA AlzBio3, INNOTEST, MSD, Simoa, and Saladax) immunoassays and the MS method in 32 individual CSF samples. Commutability was evaluated by Passing-Bablok regression and the candidate CRM termed commutable when found within the prediction interval (PI). The relative distance to the regression line was assessed. RESULTS: The neat CSF candidate CRM format was commutable for almost all method comparisons, except for the Simoa/MSD, Simoa/MS and MS/IBL where it was found just outside the 95% PI. However, the neat CSF was found within 5% relative distance to the regression line for MS/IBL, between 5% and 10% for Simoa/MS and between 10% and 15% for Simoa/MSD comparisons. CONCLUSIONS: The neat CSF candidate CRM format was commutable for 33 of 36 method comparisons, only one comparison more than expected given the 95% PI acceptance limit. We conclude that the neat CSF candidate CRM can be used for value assignment of the kit calibrators for the different Aβ42 methods.
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| 2. |
- Kuhlmann, Julia, et al.
(författare)
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CSF Aβ1-42 - an excellent but complicated Alzheimer's biomarker - a route to standardisation.
- 2017
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Ingår i: Clinica chimica acta; international journal of clinical chemistry. - : Elsevier BV. - 1873-3492. ; 467, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- The 42 amino acid form of amyloid β (Aβ1-42) in cerebrospinal fluid (CSF) has been widely accepted as a central biomarker for Alzheimer's disease. Several immunoassays for CSF Aβ1-42 are commercially available, but can suffer from between laboratory and batch-to-batch variability as well as lack of standardisation across assays. As a consequence, no general cut-off values have been established for a specific context of use (e.g., clinical diagnostics) and selection of individuals for enrolment in clinical trials (patient stratification) remains challenging. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has initiated a working group for CSF proteins (WG-CSF) to facilitate standardisation of CSF Aβ1-42 measurement results. The efforts of the IFCC WG-CSF include the development of certified reference materials (CRMs) and reference measurement procedures (RMPs) for key biomarkers. Two candidate RMPs for quantification of Aβ1-42 in CSF based on liquid chromatography tandem mass spectrometry have been developed and tested in two ring trials. Furthermore, two commutability studies including native CSF pools, artificial CSF and spiked materials have been completed. On the basis of these studies, human CSF pools containing only endogenous Aβ1-42 at three concentrations were selected as the format for future CRMs that are now being processed.
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| 3. |
- Andreasson, Ulf, 1968, et al.
(författare)
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Commutability of the certified reference materials for the standardization of beta-amyloid 1-42 assay in human cerebrospinal fluid: lessons for tau and beta-amyloid 1-40 measurements
- 2018
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 56:12, s. 2058-2066
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Tidskriftsartikel (refereegranskat)abstract
- Background: The core Alzheimer's disease cerebrospinal fluid (CSF) biomarkers total tau (T-tau), phosphorylated tau (P-tau), beta-amyloid 1-42 (A beta 42) and beta-amyloid 1-40 (A beta 40) are increasing in importance and are now part of the research criteria for the diagnosis of the disease. The main aim of this study is to evaluate whether a set of certified reference materials (CRMs) are commutable for A beta 42 and to serve as a feasibility study for the other markers. This property is a prerequisite for the establishment of CRMs which will then be used by manufacturers to calibrate their assays against. Once the preanalytical factors have been standardized and proper selection criteria are available for subject cohorts this harmonization between methods will allow for universal cut-offs to be determined. Methods: Thirty-four individual CSF samples and three different CRMs where analyzed for T-tau, P-tau, A beta 42 and A beta 40, using up to seven different commercially available methods. For A beta 40 and A beta 42 a mass spectrometry-based procedure was also employed. Results: There were strong pairwise correlations between the different methods (Spearman's p>0.92) for all investigated analytes and the CRMs were not distinguishable from the individual samples. Conclusions: This study shows that the CRMs are commutable for the different assays for A beta 42. For the other analytes the results show that it would be feasible to also produce CRMs for these. However, additional studies are needed as the concentration interval for the CRMs were selected based on A beta 42 concentrations only and did in general not cover satisfactory large concentration intervals for the other analytes.
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| 4. |
- Mollenhauer, Brit, et al.
(författare)
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Antibody-based methods for the measurement of α-synuclein concentration in human cerebrospinal fluid - method comparison and round robin study.
- 2019
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Ingår i: Journal of neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 149:1, s. 126-138
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Tidskriftsartikel (refereegranskat)abstract
- α-Synuclein is the major component of Lewy bodies and a candidate biomarker for neurodegenerative diseases in which Lewy bodies are common, including Parkinson's disease and dementia with Lewy bodies. A large body of literature suggests that these disorders are characterized by reduced concentrations of α-synuclein in cerebrospinal fluid (CSF), with overlapping concentrations compared to healthy controls and variability across studies. Several reasons can account for this variability, including technical ones, such as inter-assay and inter-laboratory variation (reproducibility). We compared four immunochemical methods for the quantification of α-synuclein concentration in 50 unique CSF samples. All methods were designed to capture most of the existing α-synuclein forms in CSF ('total' α-synuclein). Each of the four methods showed high analytical precision, excellent correlation between laboratories (R2 0.83-0.99), and good correlation with each other (R2 0.64-0.93), although the slopes of the regression lines were different between the four immunoassays. The use of common reference CSF samples decreased the differences in α-synuclein concentration between detection methods and technologies. Pilot data on an immunoprecipitation mass spectrometry (IP-MS) method isalso presented. Our results suggest that the four immunochemical methods and the IP-MS method measure similarforms of α-synuclein and that a common reference materialwould allow harmonization of results between immunoassays.
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| 5. |
- Vanderstichele, Hugo Marcel Johan, et al.
(författare)
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Optimized Standard Operating Procedures for the Analysis of Cerebrospinal Fluid Aβ42 and the Ratios of Aβ Isoforms Using Low Protein Binding Tubes
- 2016
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877. ; 53:3, s. 1121-1132
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reduced cerebrospinal fluid (CSF) concentration of amyloid-β1-42 (Aβ1-42) reflects the presence of amyloidopathy in brains of subjects with Alzheimer's disease (AD). Objective: To qualify the use of Aβ1-42/Aβ1-40 for improvement of standard operating procedures (SOP) for measurement of CSF Aβ with a focus on CSF collection, storage, and analysis. Methods: Euroimmun ELISAs for CSF Aβ isoforms were used to set up a SOP with respect to recipient properties (low binding, polypropylene), volume of tubes, freeze/thaw cycles, addition of detergents (Triton X-100, Tween-20) in collection or storage tubes or during CSF analysis. Data were analyzed with linear repeated measures and mixed effects models. Results: Optimization of CSF analysis included a pre-wash of recipients (e.g., tubes, 96-well plates) before sample analysis. Using the Aβ1-42/Aβ1-40 ratio, in contrast to Aβ1-42, eliminated effects of tube type, additional freeze/thaw cycles, or effect of CSF volumes for polypropylene storage tubes. 'Low binding' tubes reduced the loss of Aβ when aliquoting CSF or in function of additional freeze/thaw cycles. Addition of detergent in CSF collection tubes resulted in an almost complete absence of variation in function of collection procedures, but affected the concentration of Aβ isoforms in the immunoassay. Conclusion: The ratio of Aβ1-42/Aβ1-40 is a more robust biomarker than Aβ1-42 toward (pre-) analytical interfering factors. Further, 'low binding' recipients and addition of detergent in collection tubes are able to remove effects of SOP-related confounding factors. Integration of the Aβ1-42/Aβ1-40 ratio and 'low-binding tubes' into guidance criteria may speed up worldwide standardization of CSF biomarker analysis.
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| 6. |
- Vanderstichele, Hugo, et al.
(författare)
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Recommendations for cerebrospinal fluid collection for the analysis by ELISA of neurogranin trunc P75, α-synuclein, and total tau in combination with Aβ(1-42)/Aβ(1-40)
- 2017
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Ingår i: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The pathophysiology of neurodegeneration is complex. Its diagnosis requires an early identification of sequential changes in several hallmarks in the brains of affected subjects. The presence of brain pathology can be visualized in the cerebrospinal fluid (CSF) by protein profiling. It is clear that the field of Alzheimer’s disease (AD) will benefit from an integration of algorithms including CSF concentrations of individual proteins, especially as an aid in clinical decision-making or to improve patient enrolment in clinical trials. The protein profiling approach requires standard operating procedures for collection and storage of CSF which must be easy to integrate into a routine clinical lab environment. Our study provides recommendations for analysis of neurogranin trunc P75, α-synuclein, and tau, in combination with the ratio of β-amyloid Aβ(1-42)/Aβ(1-40). Methods: Protocols for CSF collection were compared with CSF derived from subjects with normal pressure hydrocephalus (n = 19). Variables included recipient type (collection, storage), tube volume, and addition of detergents at the time of collection. CSF biomarker analysis was performed with enzyme-linked immunosorbent assays (ELISAs). Data were analyzed with linear repeated measures and mixed effects models. Results: Adsorption to recipients is lower for neurogranin trunc P75, α-synuclein, and tau (<10%), as compared to Aβ(1-42). For neurogranin trunc P75 and total tau, there is still an effect on analyte concentrations as a function of the tube volume. Protocol-related differences for Aβ(1-42) can be normalized at the (pre-)analytical level using the ratio Aβ(1-42)/Aβ(1-40), but not by using the ratio Aβ(1-42)/tau. The addition of detergent at the time of collection eliminates differences due to adsorption. Conclusions: Our study recommends the use of low protein binding tubes for quantification in CSF (without additives) of all relevant CSF biomarkers. Pre-analytical factors have less effect on α-synuclein, neurogranin trunc P75, and total tau, as compared to Aβ(1-42). The ratio of Aβ(1-42)/Aβ(1-40), but not Aβ(1-42)/tau, can be used to adjust for pre-analytical differences in analyte concentrations. Our study does not recommend the inclusion of detergents at the time of collection of CSF. The present results provide an experimental basis for new recommendations for parallel analysis of several proteins using one protocol for collection and storage of CSF.
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