Fig. 5.
No detectable alterations in Aβ levels or APP processing with microglia elimination in 5xFAD mice. a–h Aβ levels from cortical (a–b, e–f) or thalamic brain homogenates (c–d, g–h) from 5xFAD mice treated with vehicle or PLX5622 (1200 ppm in chow) from 1.5 months of age to either 4 (a–d), or 7 (e–h) months of age, for both the detergent-soluble and insoluble fractions. In the 4-month-old mice, insoluble Aβ1–38 and Aβ1–40 were below detection threshold. In the 7-month-old mice, insoluble Aβ levels were plotted on log(10) scale and insoluble Aβ1–38 was below detection threshold. Two-tailed independent t-test. For 4-month-old cohort: n = 7 for 5xFAD, n = 9 for 5xFAD + PLX5622. For 7-month-old cohort: n = 7 for 5xFAD, n = 8 for 5xFAD + PLX5622. i–j Cortical homogenates of 7-month-old mice immunoprobed and quantified, respectively, for A11. Two-tailed independent t-test; n = 7 for 5xFAD, n = 8 for 5xFAD + PLX5622. Source data are provided as a Source Data file. k–l Levels of components of the amyloid-precursor protein (APP) processing pathway in cortical homogenates from 7-month-old animals (Full length APP: WT v 5xFAD, p = 0.001; PLX5622 v 5xFAD v PLX5622, p < 0.001; 5xFAD v 5xFAD + PLX5622; p = 0.020. C83: WT v 5xFAD, p < 0.001; PLX5622 v 5xFAD v PLX5622, p < 0.001. C99: WT v 5xFAD, p = 0.015; PLX5622 v 5xFAD v PLX5622 p < 0.001). Two-way ANOVA with Tukey’s post hoc test; n = 8 for Wild-type, n = 8 for PLX5622, n = 8 for 5xFAD, n = 8 for 5xFAD + PLX5622. Source data are provided as a Source Data file. M, Left panel - heatmap of log(2) fold change of genes associated with AD, including APP/Aβ production and metabolism shown for each of the 9 comparisons and the 6 comparisons between brain regions. Right panel – heatmap of the corresponding p-values for each of the comparisons. Log(2) fold change and p-values indicated by respective scale bar. n = 4 for all groups. Error bars indicate SEM