First Amyloid β1-42 Certified Reference Material for Re-calibrating Commercial Immunoassays

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2020 Aug 6

PMID 32755010

Citations 30

Authors

Sebastien Boulo

Julia Kuhlmann

Ulf Andreasson

Britta Brix

Iswariya Venkataraman

Victor Herbst

Sandra Rutz

Ekaterina Manuilova

Manu Vandijck

Filip Dekeyser

Maria Bjerke

Josef Pannee

Jean Charoud-Got

Guy Auclair

Stephane Mazoua

Gregor Pinski

Stefanie Trapmann

Heinz Schimmel

Hendrik Emons

Milena Quaglia

Erik Portelius

Magdalena Korecka

Leslie M Shaw

Mary Lame

Erin Chambers

Hugo Vanderstichele

Erik Stoops

Andreas Leinenbach

Tobias Bittner

Rand G Jenkins

Vesna Kostanjevecki

Piotr Lewczuk

Johan Gobom

Henrik Zetterberg

Ingrid Zegers

Kaj Blennow

Affiliations

Soon will be listed here.

Abstract

Introduction: Reference materials based on human cerebrospinal fluid were certified for the mass concentration of amyloid beta (Aβ)1-42 (Aβ ). They are intended to be used to calibrate diagnostic assays for Aβ .

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 Aβ mass concentrations in ERM-DA480/IFCC, ERM-DA481/IFCC, and ERM-DA482/IFCC are 0.45, 0.72, and 1.22 μg/L, respectively, with expanded uncertainties (k = 2) of 0.07, 0.11, and 0.18 μg/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 Aβ CRMs can ensure the equivalence of results between methods and across platforms for the measurement of Aβ .

Citing Articles

Development of amyloid β (1-42) certified reference material NMIJ CRM 6210-a.

Saikusa K, Kinumi T, Kato M Anal Bioanal Chem. 2025; .

PMID: 40038127 DOI: 10.1007/s00216-025-05797-0.

Application of the revised criteria for diagnosis and staging of Alzheimer's disease: Drug development and clinical practice.

Jack C, Graf A, Burnham S, Doty E, Moebius H, Montenigro P Alzheimers Dement (N Y). 2025; 10(4):e70013.

PMID: 39748835 PMC: 11694534. DOI: 10.1002/trc2.70013.

Analytical and clinical performance of eight Simoa and Lumipulse assays for automated measurement of plasma p-tau181 and p-tau217.

Wojdala A, Vanbrabant J, Bayoumy S, Antwi-Berko D, Le Bastard N, van der Flier W Alzheimers Res Ther. 2024; 16(1):266.

PMID: 39702308 PMC: 11660642. DOI: 10.1186/s13195-024-01630-5.

ADNI Biomarker Core: A review of progress since 2004 and future challenges.

Shaw L, Korecka M, Lee E, Cousins K, Vanderstichele H, Schindler S Alzheimers Dement. 2024; 21(1):e14264.

PMID: 39614747 PMC: 11773510. DOI: 10.1002/alz.14264.

Evaluation of the EUROIMMUN automated chemiluminescence immunoassays for measurement of four core biomarkers for Alzheimer's disease in cerebrospinal fluid.

Rompler K, Arendt P, Brix B, Borchardt-Loholter V, Schulz A, Busse M Pract Lab Med. 2024; 41:e00425.

PMID: 39314784 PMC: 11417521. DOI: 10.1016/j.plabm.2024.e00425.

References

Blennow K, Mattsson N, Scholl M, Hansson O, Zetterberg H . Amyloid biomarkers in Alzheimer's disease. Trends Pharmacol Sci. 2015; 36(5):297-309. DOI: 10.1016/j.tips.2015.03.002. View

Korecka M, Waligorska T, Figurski M, Toledo J, Arnold S, Grossman M . Qualification of a surrogate matrix-based absolute quantification method for amyloid-β₄₂ in human cerebrospinal fluid using 2D UPLC-tandem mass spectrometry. J Alzheimers Dis. 2014; 41(2):441-51. PMC: 4159707. DOI: 10.3233/JAD-132489. View

Bittner T, Zetterberg H, Teunissen C, Ostlund Jr R, Militello M, Andreasson U . Technical performance of a novel, fully automated electrochemiluminescence immunoassay for the quantitation of β-amyloid (1-42) in human cerebrospinal fluid. Alzheimers Dement. 2015; 12(5):517-26. DOI: 10.1016/j.jalz.2015.09.009. View

Blennow K, Hampel H, Weiner M, Zetterberg H . Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010; 6(3):131-44. DOI: 10.1038/nrneurol.2010.4. View

Shaw L, Vanderstichele H, Knapik-Czajka M, Clark C, Aisen P, Petersen R . Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol. 2009; 65(4):403-13. PMC: 2696350. DOI: 10.1002/ana.21610. View

Linnet K . Evaluation of regression procedures for methods comparison studies. Clin Chem. 1993; 39(3):424-32. View

Lautner R, Insel P, Skillback T, Olsson B, Landen M, Frisoni G . Preclinical effects of APOE ε4 on cerebrospinal fluid Aβ42 concentrations. Alzheimers Res Ther. 2017; 9(1):87. PMC: 5654097. DOI: 10.1186/s13195-017-0313-3. View

Vanderstichele H, Janelidze S, Demeyer L, Coart E, Stoops E, Herbst V . Optimized Standard Operating Procedures for the Analysis of Cerebrospinal Fluid Aβ42 and the Ratios of Aβ Isoforms Using Low Protein Binding Tubes. J Alzheimers Dis. 2016; 53(3):1121-32. PMC: 4981898. DOI: 10.3233/JAD-160286. View

Kuhlmann J, Andreasson U, Pannee J, Bjerke M, Portelius E, Leinenbach A . CSF Aβ - an excellent but complicated Alzheimer's biomarker - a route to standardisation. Clin Chim Acta. 2016; 467:27-33. DOI: 10.1016/j.cca.2016.05.014. View

10.

Boulo S, Kuhlmann J, Andreasson U, Brix B, Venkataraman I, Herbst V . First amyloid β1-42 certified reference material for re-calibrating commercial immunoassays. Alzheimers Dement. 2020; 16(11):1493-1503. PMC: 7984389. DOI: 10.1002/alz.12145. View

11.

Pannee J, Gobom J, Shaw L, Korecka M, Chambers E, Lame M . Round robin test on quantification of amyloid-β 1-42 in cerebrospinal fluid by mass spectrometry. Alzheimers Dement. 2015; 12(1):55-9. DOI: 10.1016/j.jalz.2015.06.1890. View

12.

Schimmel H, Zegers I, Emons H . Standardization of protein biomarker measurements: is it feasible?. Scand J Clin Lab Invest Suppl. 2010; 242:27-33. DOI: 10.3109/00365513.2010.493362. View

13.

Lautner R, Palmqvist S, Mattsson N, Andreasson U, Wallin A, Palsson E . Apolipoprotein E genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease. JAMA Psychiatry. 2014; 71(10):1183-91. DOI: 10.1001/jamapsychiatry.2014.1060. View

14.

Bjerke M, Portelius E, Minthon L, Wallin A, Anckarsater H, Anckarsater R . Confounding factors influencing amyloid Beta concentration in cerebrospinal fluid. Int J Alzheimers Dis. 2010; 2010. PMC: 2925386. DOI: 10.4061/2010/986310. View

15.

Hansson O, Seibyl J, Stomrud E, Zetterberg H, Trojanowski J, Bittner T . CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts. Alzheimers Dement. 2018; 14(11):1470-1481. PMC: 6119541. DOI: 10.1016/j.jalz.2018.01.010. View

16.

Broersen K, Jonckheere W, Rozenski J, Vandersteen A, Pauwels K, Pastore A . A standardized and biocompatible preparation of aggregate-free amyloid beta peptide for biophysical and biological studies of Alzheimer's disease. Protein Eng Des Sel. 2011; 24(9):743-50. DOI: 10.1093/protein/gzr020. View

17.

Vanderstichele H, Shaw L, Vandijck M, Jeromin A, Zetterberg H, Blennow K . Alzheimer disease biomarker testing in cerebrospinal fluid: a method to harmonize assay platforms in the absence of an absolute reference standard. Clin Chem. 2013; 59(4):710-2. DOI: 10.1373/clinchem.2012.201830. View

18.

Willemse E, van Uffelen K, Brix B, Engelborghs S, Vanderstichele H, Teunissen C . How to handle adsorption of cerebrospinal fluid amyloid β (1-42) in laboratory practice? Identifying problematic handlings and resolving the issue by use of the Aβ/Aβ ratio. Alzheimers Dement. 2017; 13(8):885-892. DOI: 10.1016/j.jalz.2017.01.010. View

19.

Toombs J, Paterson R, Schott J, Zetterberg H . Amyloid-beta 42 adsorption following serial tube transfer. Alzheimers Res Ther. 2014; 6(1):5. PMC: 4059346. DOI: 10.1186/alzrt236. View

20.

Verwey N, van der Flier W, Blennow K, Clark C, Sokolow S, De Deyn P . A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer's disease. Ann Clin Biochem. 2009; 46(Pt 3):235-40. DOI: 10.1258/acb.2009.008232. View