We identified lipid droplet (LD)-laden microglia in human Alzheimer's disease (AD) and 5xFAD mouse brains. We showed that these LD-rich microglia are induced by Aβ and exhibit phagocytosis deficits. Furthermore, we found that the pharmacological inhibition of a LD-related protein (diacylglycerol O-acyltransferase 2) in microglia enhances their ability to phagocytose Aβ. This study highlights the crucial role of lipids in modulating microglial function in the context of AD.
This study involved the development and use of large-scale lipidomics and metabolomics analyses using multiple reaction monitoring mass spectrometry. Using this approach, I screened over 1500 distinct lipid species across 10 major lipid categories, as well as the examination of 700 metabolites.
In another collaborative project, I extended similar lipidomic and metabolomic profiling to neurotoxic reactive astrocytes and their secreted medium. This effort resulted in the identification of phosphatidylcholines and long-chain saturated free fatty acids as astrocyte-specific neurotoxic factors in these components, respectively. This work underscores the significance of lipids, previously deemed elusive molecules, as substantial contributors to neurotoxicity in neurodegenerative processes.
This study involved the development and use of large-scale lipidomics and metabolomics analyses using multiple reaction monitoring mass spectrometry. Using this approach, I screened over 1500 distinct lipid species across 10 major lipid categories, as well as the examination of 700 metabolites.
In another collaborative project, I extended similar lipidomic and metabolomic profiling to neurotoxic reactive astrocytes and their secreted medium. This effort resulted in the identification of phosphatidylcholines and long-chain saturated free fatty acids as astrocyte-specific neurotoxic factors in these components, respectively. This work underscores the significance of lipids, previously deemed elusive molecules, as substantial contributors to neurotoxicity in neurodegenerative processes.