A simplified and sensitive method to identify Alzheimer's disease biomarker candidates using patient-derived induced pluripotent stem cells (iPSCs)

Keiro Shirotani; Kazuya Matsuo; Sumio Ohtsuki; Takeshi Masuda; Masashi Asai; Yumiko Kutoku; Yutaka Ohsawa; Yoshihide Sunada; Takayuki Kondo; Haruhisa Inoue; Nobuhisa Iwata

doi:10.1093/jb/mvx058

A simplified and sensitive method to identify Alzheimer's disease biomarker candidates using patient-derived induced pluripotent stem cells (iPSCs)

J Biochem. 2017 Dec 1;162(6):391-394. doi: 10.1093/jb/mvx058.

Authors

Keiro Shirotani^{1

2

3}, Kazuya Matsuo¹, Sumio Ohtsuki⁴, Takeshi Masuda⁴, Masashi Asai^{1

2

3}, Yumiko Kutoku⁵, Yutaka Ohsawa⁵, Yoshihide Sunada⁵, Takayuki Kondo^{3

6}, Haruhisa Inoue^{3

6}, Nobuhisa Iwata^{1

2

3}

Affiliations

¹ Department of Genome-based Drug Discovery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan.
² Unit for Dementia Research and Drug Discovery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan.
³ Core Research for Evolutional Science and Technology (CREST).
⁴ Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
⁵ Department of Neurology, Kawasaki Medical School, Okayama 701-0192, Japan.
⁶ Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan.

PMID: 28992104
DOI: 10.1093/jb/mvx058

Abstract

We developed a simplified and sensitive method to identify Alzheimer's disease (AD) biomarker candidates by a quantitative and targeted proteomic analysis (combination of liquid chromatography tandem mass spectrometry and multiplexed-multiple reaction monitoring/selected reaction monitoring analysis) of culture media from neurons differentiated from induced pluripotent stem cells (iPSCs) established from AD patients. We found that alpha-1-acid glycoprotein (ORM1) was decreased in the culture media of AD-iPSC-derived neurons, consistent with previous observations for AD patient cerebrospinal fluid, thus validating our new strategy. Moreover, our method is applicable for identifying biomarker candidates for other neurodegenerative disorders using patient-derived iPSCs.

Keywords: Alzheimer’s disease; LC-MS/MS; biomarker; iPSCs; proteomics.

MeSH terms

Alzheimer Disease / diagnosis*
Biomarkers / analysis
Chromatography, Liquid
Glycoproteins / analysis*
Humans
Induced Pluripotent Stem Cells / chemistry
Induced Pluripotent Stem Cells / pathology*
Neurons / chemistry
Neurons / pathology
Proteomics
Tandem Mass Spectrometry

Substances

Biomarkers
Glycoproteins