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Multiple reaction monitoring assay based on conventional liquid chromatography and electrospray ionization for simultaneous monitoring of multiple cerebrospinal fluid biomarker candidates for Alzheimer’s disease

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Abstract

Alzheimer’s disease (AD) is the most common type of dementia, but early and accurate diagnosis remains challenging. Previously, a panel of cerebrospinal fluid (CSF) biomarker candidates distinguishing AD and non-AD CSF accurately (>90 %) was reported. Furthermore, a multiple reaction monitoring (MRM) assay based on nano liquid chromatography tandem mass spectrometry (nLC–MS/MS) was developed to help validate putative AD CSF biomarker candidates including proteins from the panel. Despite the good performance of the MRM assay, wide acceptance may be challenging because of limited availability of nLC–MS/MS systems in laboratories. Thus, here, a new MRM assay based on conventional LC–MS/MS is presented. This method monitors 16 peptides representing 16 (of 23) biomarker candidates that belonged to the previous AD CSF panel. A 30-times more concentrated sample than the sample used for the previous study was loaded onto a high capacity trap column, and all 16 MRM transitions showed good linearity (average R2 = 0.966), intra-day reproducibility (average coefficient of variance (CV) = 4.78 %), and inter-day reproducibility (average CV = 9.85 %). The present method has several advantages such as a shorter analysis time, no possibility of target variability, and no need for an internal standard.

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Acknowledgments

We gratefully acknowledge the National Institutes of Health (R01MH59926, 2P20RR016472, 5P30RR031160), the New York State Office of Science, Technology, and Academic Research, and the Institute for the Study of Aging for support of this work.

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Authors and Affiliations

  1. Department of Chemical Engineering and Delaware Biotechnology Institute, University of Delaware, Newark, DE, 19711, USA

    Yong Seok Choi & Kelvin H. Lee

  2. College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan-Si, Chungnam, 330-714, South Korea

    Yong Seok Choi

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  1. Yong Seok Choi
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Correspondence to Yong Seok Choi.

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Choi, Y.S., Lee, K.H. Multiple reaction monitoring assay based on conventional liquid chromatography and electrospray ionization for simultaneous monitoring of multiple cerebrospinal fluid biomarker candidates for Alzheimer’s disease. Arch. Pharm. Res. 39, 390–397 (2016). https://doi.org/10.1007/s12272-015-0663-y

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