Fig. 3: Lipid and protein changes in the cerebellum in TDP-43^Q331K/Q331KTmem106b^−/− mice.

Total lipids were extracted from cerebellums of 10.0-month-old WT, TDP-43^Q331K/Q331K, Tmem106b^−/−, TDP-43^Q331K/Q331KTmem106b^−/− male mice, and lipids were analyzed by mass spectrometry (n = 6 mice per genotype). a Lipid classes identified in the cerebellum and the number of species identified in each lipid class. b Total levels (sum of all species) of the cholesterol esters (CE), diglycerides (DG), and phosphatidylcholines (PC) in the cerebellum. Data are presented as mean ± SEM (n = 6 mice per genotype). P values were determined using one-way ANOVA tests with Bonferroni’s multiple comparisons and were shown on the top of the graphs. c Heatmap was shown for the significantly changed lipid species with FDR < 0.05 and absolute log2(FC) > 0.5 in the TDP-43^Q331K/Q331K Tmem106b^−/− mice compared to the WT. Red highlighted species were also significantly altered in Tmem106b^−/− mice compared to WT. d Venn diagram showing the overlap of the upregulated and downregulated proteins between the indicated comparisons. e Volcano plots were shown for the significant changed proteins with FDR < 0.05 and absolute log2(FC) > 0.5 in the indicated comparisons. The names of the top 10 upregulated and downregulated proteins were displayed. f Heatmap illustrating the changes of the proteins that significantly affected the TDP-43^Q331K/Q331K Tmem106b^−/− cerebellum compared to the WT (FDR < 0.05 and absolute log2(FC) > 0.5). Only proteins with an intensity above 1000 are plotted in the heatmap. Red highlights the lysosomal proteins. Underlined text indicates the proteins involved in inflammation. Asterisks mark the proteins associated with lipid metabolism.