Investigating ApoE4‐mediated metabolic alteration of H4 neuroglioma cells of Alzheimer’s disease

Lu, Li; Kotowska, Anna; Kern, Stefanie; Fang, Min; Rudd, Timothy R.; Alexander, Morgan; Scurr, David; Zhu, Zheying

Abstract

Background
Metabolites and proteins in ApoE4‐carried H4 neuroglioma cells were analyzed to investigate the potential mechanism of the risk gene ApoE4 involved in Alzheimer’s disease (AD).

Method
Metabolomics of ApoE4‐carried and wild‐type H4 cells was performed by applying a novel workflow composed of Orbital trapping secondary ion mass spectrometry (OrbiSIMS) as a screening tool, followed by LC‐MS/MS targeted metabolomics for further confirming polar molecules. Proteins affected by ApoE4 were identified by performing LC‐MS‐based proteomics, followed by investigating the protein network and functional enrichment analysis using the STRING database.

Result
The initial OrbiSIMS approach has shown the advantages of detecting large numbers of metabolites with minimal sample preparation, small sample size and a relatively rapid analysis time, allowing 192 putatively annotated metabolites detected in our study. We found glycerophospholipid metabolism, aspartate, glutamate and alanine are the most affected pathways by ApoE4. Polar‐targeted metabolomics of LC‐MS/MS further revealed that the metabolism of taurine and hypotaurine is also affected by ApoE4. Besides, proteomics results suggest an overall metabolic process, RNA splicing process, and translation associated with ApoE4‐related AD development.

Conclusion
Our results have elucidated the metabolic alteration of H4 neuroglioma cells in the presence of ApoE4, supporting the hypothesis of the low ability of ApoE4 in transporting lipids and discovering two new potential pathways that may be involved in AD. In addition, proteomics analysis by LC‐MS further proved the ApoE4‐mediated dysfunction of nitrogen compound metabolism and RNA splicing process.

Citation

Lu, L., Kotowska, A., Kern, S., Fang, M., Rudd, T. R., Alexander, M., …Zhu, Z. (2023). Investigating ApoE4‐mediated metabolic alteration of H4 neuroglioma cells of Alzheimer’s disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 19(S24), Article e082458. https://doi.org/10.1002/alz.082458

• Journal Article Type: Conference Paper
• Conference Name: Alzheimer’s Association International Conference 2023
• Conference Location: Amterdam, Netherlands and online
• Acceptance Date: Feb 28, 2023
• Online Publication Date: Dec 25, 2023
• Publication Date: 2023-12
• Deposit Date: Mar 2, 2024
• Print ISSN: 1552-5260
• Electronic ISSN: 1552-5279
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: S24
• Article Number: e082458
• DOI: https://doi.org/10.1002/alz.082458
• Keywords: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Geriatrics and Gerontology, Neurology (clinical), Developmental Neuroscience, Health Policy, Epidemiology
• Public URL: https://nottingham-repository.worktribe.com/output/30411522
• Publisher URL: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.082458