나용흠 (충남대학교 분석과학기술대학원)

안현주 (충남대학교 분석과학기술대학원)

나용흠 (충남대학교 분석과학기술대학원)

정혜경 (충남대학교 분석과학기술대학원)

유재영 (충남대학교 분석과학기술대학원)

윤종현 (충남대학교 분석과학기술대학원)

윤종혁 (한국뇌연구원)

안현주 (충남대학교 분석과학기술대학원)

Gangliosides play crucial roles in neuronal functions such as synapse formation and signal transduction. Recent studies have shown their close association with neurodegenerative diseases such as Alzheimer's disease (AD). Despite their high relevance, comprehensive studies on gangliosides in relation to AD are lacking. In this study, we monitored AD-specific gangliosides in five major brain regions (hippocampus, cortex, thalamus, olfactory bulb, and cerebellum) of 3- and 6-month-old wild-type (WT) and AD mouse models (5XFAD) using UHPLC/Q-TOF-MS. By leveraging an in-house ganglioside compound database based on analytical platform previously developed by our group, we characterized approximately 90 ganglioside compositions across these five brain regions. Hierarchical clustering analysis based on ganglioside composition and relative abundance revealed grouping by brain region. Disease-specific differentiation was observed in the olfactory bulb and hippocampus at 6 months and only in the hippocampus at 3 months. The hippocampus showed distinct AD-specific differentiation at all ages, unlike the other brain regions. Notably, in the hippocampus, a significant increase was observed in certain gangliosides belonging to the B biosynthetic series (GD3, GD2, GD1b, GT1b, GQ1b) with d36:1 in AD. This increase was more pronounced at 6 months compared to 3 months, highlighting that the increase in AD-specific gangliosides also rose with age. These findings enhance the understanding of the pathophysiology of AD and provide novel insights into potential biomarkers.