Extended Data Fig. 10: Pathway enrichment analysis of neuronal layers of the cerebellum in WT and 5xFAD mouse brains.

a. 2D slice and 3D rendered views of WT and 5xFAD mouse brains displaying the distribution of phosphatidylinositol (PI) 38:5 in the hippocampus and cerebellum. b. The excitatory neuronal bodies of the cerebellum from a Nissl-stained sagittal brain section from the Allen Brain Atlas and Allen Reference Atlas, – Mouse Brain, Allen Mouse Brain Atlas, mouse.brain-map.org and atlas.brain-map.org (left) and pixels corresponding to these regions were extracted (right) for targeted analysis. c. Pathway enrichment analysis was performed on metabolomics (left) and lipidomics (right) datasets extracted from these pixels. Metabolomics pathway enrichment was conducted using MetaboAnalyst using the hypergeometric test and adjusted for multiple comparison (bonferroni correction) highlighting key pathways such as the transfer of acetyl groups into mitochondria, the Warburg effect, and the citric acid cycle based on -log₁₀(pvalue). Lipid ontology enrichment using the one-sided Kolmogorov-Smirnov test and adjusted for multiple comparison (bonferroni correction) was performed using Lipid Ontology (LION) pathway analysis, identifying significant lipid categories related to bilayer thickness and lateral diffusion properties based on -log₁₀(pvalue).