| 1. |
- 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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| 2. |
- Andreasson, Ulf, 1968, et al.
(författare)
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Multiplexing and multivariate analysis in neurodegeneration.
- 2012
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Ingår i: Methods (San Diego, Calif.). - : Elsevier BV. - 1095-9130 .- 1046-2023. ; 56:4, s. 464-70
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Tidskriftsartikel (refereegranskat)abstract
- Limited sample volume is often an obstacle in clinical research and one way to circumvent this is to use multiplex techniques where several different analytes are simultaneously measured. There is a multitude of different platforms that can be used for multiplexing and their uniqueness and similarities will be described. Multivariate analysis is a powerful tool for extracting information from multiplex data. An introduction to one such algorithm is presented followed by examples from the literature, in the field of neurodegeneration, where multiplex and multivariate methods have been used.
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| 3. |
- 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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| 4. |
- Boulo, S., et al.
(författare)
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First amyloid β1-42 certified reference material for re-calibrating commercial immunoassays
- 2020
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:11, s. 1493-1503
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Reference materials based on human cerebrospinal fluid were certified for the mass concentration of amyloid beta (Aβ)1-42 (Aβ42). They are intended to be used to calibrate diagnostic assays for Aβ42. Methods: The three certified reference materials (CRMs), ERM-DA480/IFCC, ERM-DA481/IFCC and ERM-DA482/IFCC, were prepared at three concentration levels and characterized using isotope dilution mass spectrometry methods. Roche, EUROIMMUN, and Fujirebio used the three CRMs to re-calibrate their immunoassays. Results: The certified Aβ42 mass concentrations in ERM-DA480/IFCC, ERM-DA481/IFCC, and ERM-DA482/IFCC are 0.45, 0.72, and 1.22μg/L, respectively, with expanded uncertainties (k=2) of 0.07, 0.11, and 0.18μg/L, respectively. Before re-calibration, a good correlation (Pearson's r>0.97), yet large biases, were observed between results from different commercial assays. After re-calibration the between-assay bias was reduced to<5%. Discussion: The Aβ42 CRMs can ensure the equivalence of results between methods and across platforms for the measurement of Aβ42. © 2020 the Alzheimer's Association
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| 5. |
- 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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| 6. |
- Leinenbach, Andreas, et al.
(författare)
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Mass spectrometry-based candidate reference measurement procedure for quantification of amyloid-β in cerebrospinal fluid.
- 2014
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Ingår i: Clinical chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 60:7, s. 987-94
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) amyloid-β (Aβ42) is a well-established biomarker for Alzheimer disease. Several immunoassays for Aβ42 exist but differ in absolute concentrations and may suffer from matrix interference, thereby hampering interlaboratory comparisons and the use of general cutoff levels. Together with the IFCC Working Group on CSF Proteins, we developed a candidate reference measurement procedure (RMP) for Aβ42.
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| 7. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Reference measurement procedures for Alzheimer's disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid β42.
- 2012
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Ingår i: Biomarkers in medicine. - : Future Medicine Ltd. - 1752-0371 .- 1752-0363. ; 6:4, s. 409-17
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in clinical settings, research and drug trials. However, their broad-scale use on different technology platforms is hampered by the lack of standardization at the level of sample handling, determination of concentrations of analytes and the absence of well-defined performance criteria for in vitro diagnostic or companion diagnostic assays, which influences the apparent concentration of the analytes measured and the subsequent interpretation of the data. There is a need for harmonization of CSF AD biomarker assays that can reliably, across centers, quantitate CSF biomarkers with high analytical precision, selectivity and stability over long time periods. In this position paper, we discuss reference procedures for the measurement of CSF AD biomarkers, especially amyloid β42 and tau. We describe possible technical approaches, focusing on a selected reaction monitoring mass spectrometry assay as a candidate reference method for quantification of CSF amyloid β42.
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| 8. |
- Pannee, Josef, 1979, et al.
(författare)
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Reference measurement procedure for CSF amyloid beta (Aβ)1–42 and the CSF Aβ1–42/Aβ1–40 ratio – a cross-validation study against amyloid PET
- 2016
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 139:4, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- A clinical diagnosis of Alzheimer's disease is currently made on the basis of results from cognitive tests in combination with medical history and general clinical evaluation, but the peptide amyloid-beta (Aβ) in cerebrospinal fluid (CSF) is increasingly used as a biomarker for amyloid pathology in clinical trials and in recently proposed revised clinical criteria for Alzheimer's disease. Recent analytical developments have resulted in mass spectrometry (MS) reference measurement procedures for absolute quantification of Aβ1–42 in CSF. The CSF Aβ1–42/Aβ1–40 ratio has been suggested to improve the detection of cerebral amyloid deposition, by compensating for inter-individual variations in total Aβ production. Our aim was to cross-validate the reference measurement procedure as well as the Aβ1–42/Aβ1–40 and Aβ1–42/Aβ1–38 ratios in CSF, measured by high-resolution MS, with the cortical level of Aβ fibrils as measured by amyloid (18F-flutemetamol) positron emission tomography (PET). We included 100 non-demented patients with cognitive symptoms from the Swedish BioFINDER study, all of whom had undergone both lumbar puncture and 18F-flutemetamol PET. Comparing CSF Aβ1–42 concentrations with 18F-flutemetamol PET showed high concordance with an area under the receiver operating characteristic curve of 0.85 and a sensitivity and specificity of 82% and 81%, respectively. The ratio of Aβ1–42/Aβ1–40 or Aβ1–42/Aβ1–38 significantly improved concordance with an area under the receiver operating characteristic curve of 0.95 and a sensitivity and specificity of 96% and 91%, respectively. These results show that the CSF Aβ1–42/Aβ1–40 and Aβ1–42/Aβ1–38 ratios using the described MS method are strongly associated with cortical Aβ fibrils measured by 18F-flutemetamol PET. (Figure presented.).
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| 9. |
- Pannee, Josef, 1979, et al.
(författare)
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The global Alzheimer's Association round robin study on plasma amyloid beta methods
- 2021
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Blood-based assays to measure brain amyloid beta (A beta) deposition are an attractive alternative to the cerebrospinal fluid (CSF)-based assays currently used in clinical settings. In this study, we examined different blood-based assays to measure A beta and how they compare among centers and assays. Methods Aliquots from 81 plasma samples were distributed to 10 participating centers. Seven immunological assays and four mass-spectrometric methods were used to measure plasma A beta concentrations. Results Correlations were weak for A beta 42 while A beta 40 correlations were stronger. The ratio A beta 42/A beta 40 did not improve the correlations and showed weak correlations. Discussion The poor correlations for A beta 42 in plasma might have several potential explanations, such as the high levels of plasma proteins (compared to CSF), sensitivity to pre-analytical sample handling and specificity, and cross-reactivity of different antibodies. Different methods might also measure different pools of plasma A beta 42. We, however, hypothesize that greater correlations might be seen in future studies because many of the methods have been refined during completion of this study.
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