Spatially Resolved Lipid Composition of the Human Brain Cortical Layers

A better understanding of neocortical architecture provides a means for its functional elucidation. In this study, we focused on the analysis of the lipidome composition in two human neocortical regions using laser-capture microdissection combined with mass spectrometry and mass spectrometry imaging. Among the 312 lipids detected in tissue samples representing discrete neocortical layers (L1, L3, and L5), three-quarters showed significant differences in abundance among layers, forming distinct patterns. Lipid distribution among these patterns depended on both the lipids' biochemical class and their fatty acid residue length and unsaturation. The assignment of lipids to cell types using spatial transcriptomics data suggested biological underpinnings of these patterns. Collected mass spectrometry imaging data further allowed for the reconstruction of lipid spatial distribution patterns across neocortical layers. These results reveal a complex relationship between lipids' biochemical properties and neocortical histological features, laying a foundation for further studies on the lipidome architecture of the human brain.