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CSF A beta(1-42) - an excellent but complicated Alzheimer's biomarker - a route to standardisation

Kuhlmann, J; Andreasson, U; Pannee, J; Bjerke, M; Portelius, E; Leinenbach, A; Bittner, T; ... Blennow, K; + view all (2017) CSF A beta(1-42) - an excellent but complicated Alzheimer's biomarker - a route to standardisation. Clinica Chimica Acta , 467 pp. 27-33. 10.1016/j.cca.2016.05.014. Green open access

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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.

Type: Article
Title: CSF A beta(1-42) - an excellent but complicated Alzheimer's biomarker - a route to standardisation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cca.2016.05.014
Publisher version: http://doi.org/10.1016/j.cca.2016.05.014
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Alzheimer's disease, Aβ1–42, Cerebrospinal fluid, Reference measurement procedure, Certified reference material
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10057931
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