Mass spectrometry-based ganglioside profiling provides potential insights into Alzheimer's disease development

Hua Li; Yilian Liu; Zhe Wang; Yuping Xie; Lijun Yang; Yanni Zhao; Ruijun Tian

doi:10.1016/j.chroma.2022.463196

Mass spectrometry-based ganglioside profiling provides potential insights into Alzheimer's disease development

J Chromatogr A. 2022 Aug 2:1676:463196. doi: 10.1016/j.chroma.2022.463196. Epub 2022 Jun 3.

Authors

Hua Li¹, Yilian Liu², Zhe Wang³, Yuping Xie⁴, Lijun Yang⁵, Yanni Zhao⁶, Ruijun Tian⁷

Affiliations

¹ SUSTech Core Research Facilities, Southern University of Science and Technology, Shenzhen, 518055 China.
² Department of Chemistry, College of Science, Southern University of Science and Technology, Shenzhen, 518055 China.
³ School of Food and Biological Engineering, Shaanxi University of Science & Technology, Xi'an 710021, China.
⁴ National Center for Protein Sciences Beijing, State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing 102206 China.
⁵ Department of Chemistry, College of Science, Southern University of Science and Technology, Shenzhen, 518055 China; Department of Oncology, The First Affiliated Hospital of SUSTech and Shenzhen People's Hospital, Shenzhen, 518020, China.
⁶ School of Food and Biological Engineering, Shaanxi University of Science & Technology, Xi'an 710021, China. Electronic address: Zhaoyanni@sust.edu.cn.
⁷ Department of Chemistry, College of Science, Southern University of Science and Technology, Shenzhen, 518055 China. Electronic address: tianrj@sustech.edu.cn.

PMID: 35716462
DOI: 10.1016/j.chroma.2022.463196

Abstract

Gangliosides are a family of glycosphingolipids which are particularly enriched in the nervous system. They play crucial roles in neuroprotection and neurological diseases. Alzheimer's disease (AD) is a neurodegenerative disease with cognitive, judgment and memory dysfunction. In this study, a mass spectrometry-based data-dependent acquisition method assisted with fragmentation characteristics screening by computer algorithm was developed for qualitative and quantitative analysis of gangliosides at low concentration. The developed method was applied to obtain detailed ganglioside species content in hippocampus of model mice (APPswe/PS1dE9 transgenic mice) with AD at 3- to 8-month-old. Up-regulated acetylated and N-acetylgalactosaminylated ganglioside species, and the down-regulated major gangliosides were observed with the development of AD from early to late stage. We speculated that deterioration of AD may be related to the acetylation/N-acetylgalactosaminylation transformation of complex gangliosides due to the inhibition of GD3 synthase activity. Moreover, the ganglioside species di-O-Ac-GT1a (d36:1), O-Ac-GD1b (d36:1) and O-Ac-GD1b (d36:0) were considered as the time-coursed biomarkers, and O-Ac-GT1a (d36:2) could be a candidate for early diagnosis of AD.

Keywords: APP/PS1 transgenic mice; Alzheimer's disease; Biomarkers; Data-dependent acquisition; Gangliosides.

MeSH terms

Alzheimer Disease*
Animals
Gangliosides / analysis
Mass Spectrometry
Mice
Mice, Transgenic
Neurodegenerative Diseases*

Substances

Gangliosides