Submission ID 94365
| Poster Code | HR-P-98 |
|---|---|
| Title of Abstract | Increased simple gangliosides associated with amyloid plaque deposition in the aged transgenic mouse model of Alzheimer's Disease |
| Abstract Submission | Alzheimer's Disease (AD) is a progressive neurodegenerative disease accounting for two-thirds of all dementia cases, and aging poses the strongest risk factor for AD. Beyond the amyloid hypothesis, lipid dysregulation has been increasingly recognized as a core component of AD pathology. Gangliosides are glycosphingolipids that account for 10% of the total lipid content in the central nervous system. Complex gangliosides GM1 and GD1a are highly abundant ganglioside in the adult brain and exerts neuroprotective effects; in contrast, the accumulation of simple gangliosides GM2 and GM3 has been associated with toxicity and neurodegeneration. Ganglioside dysregulation has been observed in pre-clinical and clinical aging and AD. However, gaps in knowledge still exist on whether dysregulated ganglioside is the cause or a consequence of beta-amyloid deposition. Thus, we aim to comprehensively characterize the progression of ganglioside dysregulation in the APP/PS1 transgenic mouse model of AD that develops age-dependent amyloid plaques. Methods: Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is performed on wildtype and APP/PS1 mice at 4, 8, 12, and 18 months to detect gangliosides across neuroanatomical regions. Results: Wildtype and transgenic mice demonstrate an age-dependent increase in GM1 across white and grey matter regions. Significantly higher levels of GM2 and GM3 were observed in transgenic mice at 12 and 18 months compared to age-matched controls in the cortex and dentate gyrus of the hippocampus. GM2 and GM3 are highly clustered on MALDI imaging and overlay with amyloid plaque-positive regions. Significance: This work is the first to demonstrate that exacerbated ganglioside dysregulation with aging is spatiotemporally associated with amyloid plaques using sophisticated imaging mass spectrometry and reveals mechanistic insights underlying lipid regulation in AD. |
| Please indicate who nominated you | Dr. Shawn Whitehead |
| What Canadian Institutes of Health Research (CIHR) institute is your research most closely aligned? | Aging Neurosciences, Mental Health and Addiction |
| What Canadian Institutes of Health Research (CIHR) pillar of health research does your research fall under? | Biomedical |
| PDF of abstract | No file |
| Presenter and Author(s) | Wenxuan Wang Shawn Whitehead Wenxuan Wang |
