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Absolute Quantification of Aβ1-42 in CSF Using a Mass Spectrometric Reference Measurement Procedure.

Pannee, J; Blennow, K; Zetterberg, H; Portelius, E; (2017) Absolute Quantification of Aβ1-42 in CSF Using a Mass Spectrometric Reference Measurement Procedure. J Vis Exp (121) , Article e55386. 10.3791/55386.

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Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly and accounts for 60-80% of all cases of dementia. Currently, the diagnosis of AD is based on cognitive tests and mental state exams, but the peptide amyloid-beta (Aβ) in cerebrospinal fluid (CSF) is increasingly used in clinical trials and settings. As for most protein and peptide biomarkers, quantification is performed using antibody-based techniques, such as enzyme-linked immunosorbent assay (ELISA). However, intra- and inter-laboratory variability in these assays hamper its use as a diagnostic marker in clinical routine. An antibody-independent Reference Measurement Procedure (RMP) was developed based on solid-phase extraction (SPE) and liquid chromatography (LC)-tandem mass spectrometry (MS/MS), where stable, isotope-labeled Aβ peptides were used as internal standards, enabling absolute quantification. A high-resolution quadrupole-orbitrap hybrid instrument was used for the measurements. The method allows for the quantification of CSF Aβ1-42 between 150-4,000 pg/mL.

Type: Article
Title: Absolute Quantification of Aβ1-42 in CSF Using a Mass Spectrometric Reference Measurement Procedure.
Location: United States
DOI: 10.3791/55386
Publisher version: http://dx.doi.org/10.3791/55386
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: Medicine, Alzheimer's disease, Amyloid Beta Peptides, Cerebrospinal Fluid, Mass Spectrometry, Liquid Chromatography, Absolute Quantification, Reference Measurement Procedure.
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology
UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Molecular Neuroscience
URI: http://discovery.ucl.ac.uk/id/eprint/1549762
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