| 1. |
- 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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| 2. |
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| 3. |
- Lifke, V., et al.
(författare)
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Elecsys® Total-Tau and Phospho-Tau (181P) CSF assays: Analytical performance of the novel, fully automated immunoassays for quantification of tau proteins in human cerebrospinal fluid
- 2019
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120. ; 72, s. 30-38
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Tidskriftsartikel (refereegranskat)abstract
- Background: Total tau (tTau) and phosphorylated 181P tau (pTau) are supportive diagnostic cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease. Manual CSF tau assays are limited by lot-to-lot and between-laboratory variability and long incubation/turnaround times. Elecsys® Total-Tau CSF and Phospho-Tau (181P) CSF immunoassays were developed for fully automated cobas e analyzers, allowing broader access in clinical practice and trials. Methods: Analytical performance, reproducibility, method comparisons with commercially available assays, and lot-to-lot and platform comparability (cobas e 601/411) of the Elecsys® CSF assays were assessed. Tau distributions and concentration ranges were evaluated in CSF samples from two clinical cohorts. Results: Both assays showed high sensitivity (limit of quantitation [LoQ]: 63 pg/mL [tTau]; 4 pg/mL [pTau]) and linearity over the measuring range (80–1300 pg/mL; 8–120 pg/mL), which covered the entire concentration range measured in clinical samples. Lot-to-lot and platform comparability demonstrated good consistency (Pearson's r: 0.998; 1.000). Multicenter evaluation coefficients of variation (CVs): repeatability, < 1.8%; intermediate precision, < 2.8%; between-laboratory variability, < 2.7% (both assays); and total reproducibility, < 6.7% (tTau) and < 4.7% (pTau). Elecsys® CSF assays demonstrated good correlation with commercially available tau assays. Conclusions: Elecsys® Total-Tau CSF and Phospho-Tau (181P) CSF assays demonstrate good analytical performance with clinically relevant measuring ranges; data support their use in clinical trials and practice. © 2019
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| 4. |
- Palmqvist, Sebastian, et al.
(författare)
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An accurate fully automated panel of plasma biomarkers for Alzheimer's disease
- 2023
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:4, s. 1204-1215
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Tidskriftsartikel (refereegranskat)abstract
- Introduction There is a great need for fully automated plasma assays that can measure amyloid beta (A beta) pathology and predict future Alzheimer's disease (AD) dementia. Methods Two cohorts (n = 920) were examined: Panel A+ (n = 32 cognitively unimpaired [CU], n = 106 mild cognitive impairment [MCI], and n = 89 AD) and BioFINDER-1 (n = 461 CU, n = 232 MCI). Plasma A beta 42/A beta 40, phosphorylated tau (p-tau)181, two p-tau217 variants, ApoE4 protein, neurofilament light, and GFAP were measured using Elecsys prototype immunoassays. Results The best biomarker for discriminating A beta-positive versus A beta-negative participants was A beta 42/A beta 40 (are under the curve [AUC] 0.83-0.87). Combining A beta 42/A beta 40, p-tau181, and ApoE4 improved the AUCs significantly (0.90 to 0.93; P< 0.01). Adding additional biomarkers had marginal effects (Delta AUC <= 0.01). In BioFINDER, p-tau181, p-tau217, and ApoE4 predicted AD dementia within 6 years in CU (AUC 0.88) and p-tau181, p-tau217, and A beta 42/A beta 40 in MCI (AUC 0.87). Discussion The high accuracies for A beta pathology and future AD dementia using fully automated instruments are promising for implementing plasma biomarkers in clinical trials and clinical routine.
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| 5. |
- Rabe, C., et al.
(författare)
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Clinical performance and robustness evaluation of plasma amyloid-beta(42/40) prescreening
- 2023
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:4, s. 1393-1402
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Further evidence is needed to support the use of plasma amyloid beta (A beta) biomarkers as Alzheimer's disease prescreening tools. This study evaluated the clinical performance and robustness of plasma A beta(42)/A beta(40) for amyloid positivity prescreening. Methods Data were collected from 333 BioFINDER and 121 Alzheimer's Disease Neuroimaging Initiative study participants. Risk and predictive values versus percentile of plasma A beta(42)/A beta(40) evaluated the actionability of plasma A beta(42)/A beta(40), and simulations modeled the impact of potential uncertainties and biases. Amyloid PET was the brain amyloidosis reference standard. Results Elecsys plasma A beta(42)/A beta(40) could potentially rule out amyloid pathology in populations with low-to-moderate amyloid positivity prevalence. However, simulations showed small measurement or pre-analytical errors in A beta(42) and/or A beta(40) cause misclassifications, impacting sensitivity or specificity. The minor fold change between amyloid PET positive and negative cases explains the biomarkers low robustness. Discussion Implementing plasma A beta(42)/A beta(40) for routine clinical use may pose significant challenges, with misclassification risks. Highlights Plasma A beta(42)/A beta(40) ruled out amyloid PET positivity in a setting of low amyloid-positive prevalence. Including (pre-) analytical errors or measurement biases caused misclassifications. Plasma A beta(42)/A beta(40) had a low inherent dynamic range, independent of analytical method. Other blood biomarkers may be easier to implement as robust prescreening tools.
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| 6. |
- Shaw, L. M., et al.
(författare)
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Method comparison study of the Elecsys® β-Amyloid (1–42) CSF assay versus comparator assays and LC-MS/MS
- 2019
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120. ; 72:October, s. 7-14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease (AD) biomarkers, such as cerebrospinal fluid (CSF) amyloid-β (1–42; Aβ42), can provide high diagnostic accuracy. Several immunoassays are available for Aβ42 quantitation, but standardisation across assays remains an issue. We compared the Elecsys® β-Amyloid (1–42) CSF assay with three assays and two liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. Methods: Three method comparison studies evaluated the correlation between the Elecsys® β-Amyloid (1–42) CSF assay versus: INNOTEST® β-AMYLOID(1–42) (860 samples) and the Roche Diagnostics-developed LC-MS/MS method (250 samples); INNO-BIA AlzBio3 and the University of Pennsylvania (UPenn)-developed LC-MS/MS method (250 samples); and ADx-EUROIMMUN Beta-Amyloid (1–42) enzyme-linked immunosorbent assay (ELISA) (49 samples). Results: High correlation was demonstrated between Elecsys® β-Amyloid (1–42) CSF and comparator assays: INNOTEST® β-AMYLOID(1–42) (Spearman's ρ, 0.954); INNO-BIA AlzBio3 (Spearman's ρ, 0.864); ADx-EUROIMMUN Beta-Amyloid (1–42) ELISA (Pearson's r, 0.925). Elecsys® assay and LC-MS/MS measurements were highly correlated: Pearson's r, 0.949 (Roche Diagnostics-developed method) and 0.943 (UPenn-developed method). Conclusion: Findings from this multicentre evaluation further support use of the Elecsys® β-Amyloid (1–42) CSF assay to aid AD diagnosis. CSF-based certified reference materials should improve agreement across assays and mass spectrometry-based methods, which is essential to establish a global uniform CSF Aβ42 cut-off to detect amyloid pathology. © 2019
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