Fig. 4.

Lipid metabolism is dysregulated in AD and CMS121 affects several lipid classes in mouse cortex. A. Random forest analysis of the top 30 metabolites indicates the importance of lipids in the separation of the different treatment groups. B. In general, metabolites classified as lipids are more elevated in untreated AD mice than CMS121-treated AD mice. C. Levels of endocannabinoids, fatty acids, PUFAs and ceramides are most clearly affected by CMS121. Eicosanoids, metabolites related to fatty acid (FA) metabolism, lysophospholipids and sphingolipids are not significantly altered in AD or affected by CMS121 treatment. Lipid levels are expressed as relative levels, normalized against untreated wildtype mice (WT). Statistical significance is determined by the Wilcoxon matched-pairs signed rank test. Cortices of 5 animals per treatment group were analyzed; each datapoint represents the average relative level of a specific metabolite. Only the most important lipid groups are presented. The entire metabolomics data set is available via https://data.mendeley.com/datasets/v6gjkzggfr/draft?a=587e71a7-f962-414f-869f-54f4ed7009d4https://doi.org/10.17632/v6gjkzggfr.1. D-E. Palmitate levels (D) as well as protein levels of FASN (see also blot below graph) (E), support a general increase in lipid levels in AD brains. Results are expressed as mean ± SEM for relative protein levels, and as box and min. to max. whisker plots for palmitate (*p<0.05, **p<0.01, one-way ANOVA, n = 5–6).