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

• Published in: Journal of Chromatography A Vol. 1676; p. 463196
• Main Authors: Li, Hua, Liu, Yilian, Wang, Zhe, Xie, Yuping, Yang, Lijun, Zhao, Yanni, Tian, Ruijun
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 02.08.2022
• Subjects: algorithms; Alzheimer disease; Alzheimer's disease; APP/PS1 transgenic mice; Biomarkers; chromatography; cognition; computers; Data-dependent acquisition; early diagnosis; Gangliosides; hippocampus; mass spectrometry; memory disorders; neurodegenerative diseases; neuroprotective effect; quantitative analysis; Biomarkers; Data-dependent acquisition; APP/PS1 transgenic mice; Gangliosides; Alzheimer's disease
• ISSN: 0021-9673
• DOI: 10.1016/j.chroma.2022.463196

•A novel mass spectrometry-based method was developed for qualitative and quantitative analysis of gangliosides.•Detailed ganglioside species content in hippocampus of model mice with Alzheimer's disease at early to late stage were obtain.•Up-regulated acetylated and N-acetylgalactosaminylated ganglioside species, and the down-regulated major gangliosides were observed with the deterioration of Alzheimer's disease.•Four acetylated ganglioside species were screened as the time-coursed biomarkers or early diagnostic marker. 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.