Reference Material for Amyloid Beta 1-40 in Human CSF - Joint Initiative of the University of Pennsylvania, JRC and IFCC

Sep 30, 2026

Uploaded by James

Background: Numerous studies show the CSF amyloid beta 42/amyloid beta 40 concentration ratio improves Alzheimer’s disease pathology detection. The IFCC initiates standardization of CSF Aβ40 measurement, building on prior work for Aβ42, to create commutable Aβ40 certified reference materials (CRMs) for assay calibration. Method: An antibody-independent reference method procedure uses guanidine hydrochloride and solid phase extraction, with LC/MS/MS Aβ40 detection. Certified CRM target values are assigned by JRC and confirmed by multiple MS-based laboratories. Result: Existing Aβ42 CRMs are unsuitable for Aβ40 due to a narrow Aβ40 range; new Aβ40 CRMs are in progress.

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CategoryHealthcare

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Abstract

Background

Method

Result

Conclusion

DOI: 10. 1002/alz70856_105152 BIOMARKERS POSTER PRESENTATION BIOMARKERS (NON-NEUROIMAGING) Reference Material for Amyloid Beta 1-40 in Human CSF: Joint Initiative of the University of Pennsylvania, JRC and IFCC Magdalena Korecka1 Vanya Uzunova2 Vincent Delatour3 Henrik Zetterberg4 Leslie M. Shaw5 1 Perelman School of Medicine, University of Pennsylvania, Department of Pathology and Laboratory Medicine, Philadelphia, PA, USA 2 European Commission, Joint Research Centre, Geel, Belgium 3 Laboratoire national de métrologie etd’essais, Paris, France 4 Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy atthe University of Gothenburg, Mölndal, Västra Götalands län, Sweden 5 Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Correspondence Magdalena Korecka, Perelman School of Medicine, University of Pennsylvania, Department of Pathology and Laboratory Medicine, Philadelphia, PA, USA. Email: [korecka@pennmedicine.upenn.edu](korecka@pennmedicine.upenn.edu) Abstract Background: Numerous studies have shown that the concentration ratio of CSF amyloid beta 42/amyloid beta 40 rather than the absolute value of CSFAβ42, provides greater accuracy for detection of Alzheimer’s disease pathology. The IFCC has recently initiated the standardization of CSFAβ40 measurement, as previously done forAβ42. The joint efforts of the IFCC, JRC, and the ADNI Biomarker Core at UPenn focus on the development, characterization, and commutability of Aβ40 certified reference materials (CRMs), utilizing reference method procedure (RMP) developed at the ADNI Biomarker Core at UPenn (JRC database: C16RMP2R). The goal is to develop CSF-based CRMs with Aβ40 concentration ranging from 2-16 ug/mL based on IVD manufacturers’ recommendation. The CRMs will be used to calibrate diagnostic assays for measurement of Aβ40 in CSF to obtain agreement across different measurement procedures. This agreement is essential to establish cut-off values and select participants for clinical trials. Method: The RMP is an antibody-independent methodology employing treatment with guanidine hydrochloride and solid phase extraction for sample purification and LC/MS/MS for Aβ40 detection (Korecka et al. JAD 2014 and Clin Chem 2020). The common calibrant produced by the JRC value and assigned by JRC, LNE, and LGCis a primary calibrator which will be used to calibrate the RMP. The target values of Aβ40 CRMs will be certified by 4-5 laboratories using their MS-based RMPs and the commutability will involve 8-10 laboratories with different techniques. Result: Aβ40 calibrant produced by JRC has a value assigned of 0.109 ± 0.005 mg/g. The mean±SD concentration ofAβ40measured at theADNI Biomarker CoreatUPenn in 3 available Aβ42 CRMs are presented in Table 1. Currently, 3 centers are planning to participate in the characterization step: the University of Gothenburg, the University of Ulm, and the UPenn. Roche, Euroimmun, ADx, Fujirebio, IBL, Quanterix, have stated plans to participate in the commutability step. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Alzheimer’s Association. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association. Alzheimer’s Dement. 2025;21(Suppl. 2):e105152. [https://doi.org/10.1002/alz70856_105152](https://doi.org/10.1002/alz70856_105152) wi[leyonlinelibrary.com/journal/alz](leyonlinelibrary.com/journal/alz) 1of2 BIOMARKERS Conclusion: The 3 available Aβ42 CRMs cannot be used asAβ40 CRMs since they have avery narrow range of Aβ40 concentration (Table 1). New CSF-based Aβ40 CRMs are needed, and the efforts are underway. The project should be completed this year.

FAQs

Why is the CSF Aβ42/Aβ40 ratio important for Alzheimer’s disease detection?

Studies indicate the concentration ratio provides greater accuracy than using the absolute value of CSF Aβ42 alone for detecting Alzheimer’s disease pathology.

What is the planned reference method for Aβ40 measurement in CSF?

The reference method procedure is antibody-independent, using guanidine hydrochloride and solid phase extraction for purification, followed by LC/MS/MS for Aβ40 detection.

Can existing Aβ42 CRMs be used as Aβ40 CRMs? Why or why not?

No. The available Aβ42 CRMs cannot serve as Aβ40 CRMs because they have a very narrow Aβ40 concentration range, so new CSF-based Aβ40 CRMs are required.

Sep 30, 2026

Uploaded by James