Fig. 4: Microglia from female APP/PS1 mice shift their metabolism towards glycolysis.

a, b NanoString analysis indicated that Hk2, Pfkfb3, Gapdh, Pgk1 and Pgam1 were upregulated in cells from APP/PS1, compared with WT, mice (*p < 0.05; **p < 0.01; ***p < 0.001; n = 6) with some changes significantly greater in female APP/PS1 mice compared with males (^§p < 0.05; ^§§p < 0.01). Expression is displayed on a log 10 scale from blue (low expression) to red (high expression). c ECAR was increased in microglia from female APP/PS1 mice with a significant increase in glycolysis in microglia from female APP/PS1 (n = 11), compared with female WT (n = 14), mice (***p < 0.001) and male APP/PS1 mice (^§§p < 0.01; n = 4) and also male WT mice (n = 8). d Lactate was increased in microglia from female APP/PS1 mice (n = 6) compared with male APP/PS1 mice (^§p < 0.05; n = 5). e, f No genotype- or sex-related changes were observed in other intermediate metabolites of glycolysis (n = 6 except for DHAP where n = 5). Minimal changes were observed in intermediate metabolites of the TCA (Supplementary Fig. 3) although marked sex-related differences were identified in amino acids generated from intermediate metabolites of glycolysis and the TCA (Supplementary Fig. 3). The changes in b, d and f are relative to values in WT males. Data, expressed as means ± SEM, were analysed by 2-way ANOVA and Tukey’s post hoc multiple comparison test.