Multiplatform Lipid Analysis of the Brain of Aging Mice by Mass Spectrometry

Lipids are critical to brain structure and function, accounting for approximately 50% of its dry weight. However, the impact of aging on brain lipids remains poorly characterized. To address this, here we applied three complementary mass spectrometry techniques: multiple reaction monitoring (MRM) profiling, untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS), and desorption electrospray ionization-MS imaging (DESI-MSI). We used brains from mice of three age groups: adult (3–4 months), middle-aged (10 months), and old (19–21 months). Phospholipids such as phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol were more abundant, while phosphatidylinositol and phosphatidylserine were reduced in old mice compared to adults or middle-aged mice. Key lipids such as polyunsaturated fatty acids, including DHA, AA, HexCer, SHexCer, and SM, were among the most abundant lipids in aged brains. DESI-MSI revealed spatial lipid distribution patterns consistent with findings from MRM profiling and LC-MS/MS. Integration of lipidomic data with the recently published proteomics data from the same tissues highlighted changes in proteins and phosphorylation levels of several proteins associated with Cer, HexCer, FA, PI, SM, and SHexCer metabolism, aligning with the multiplatform lipid surveillance. These findings shed insight into age-dependent brain lipid changes and their potential contribution to age-related cognitive decline.