APOE4 effects on neuronal transcriptome and neuritic density. (A) Volcano plot showing the DEGs identified in excitatory neurons of E3F (red) and E4F (cyan) mice at 9–12 vs. 2–3 mo of age. (B) Plots comparing the average log₂ fold-change of the common DEGs identified in excitatory neurons of both E3F (x axis) and E4F (y axis) mice (9–12- vs. 2–3-mo-old mice). (C) Bar charts reporting the number of DEGs encoding for proteins with known function in each functional class, as exclusively identified in excitatory neurons of 9–12- vs. 2–3-mo-old E4F mice only (134 DEGs), but not in 9–12- vs. 2–3-mo-old E3F mice. (D) Volcano plot showing the DEGs identified in inhibitory neurons of E3F (red) and E4F (cyan) mice at 9–12 vs. 2–3 mo of age. (E) Plots comparing the average log₂ fold-change of the common DEGs identified in inhibitory neurons of both E3F (x axis) and E4F (y axis) mice (9–12 vs. 2–3 mo of age). (F) Bar charts reporting the number of DEGs encoding for proteins with known function in each functional class, as exclusively identified in inhibitory neurons of 9–12- vs. 2–3-mo-old E4F mice only (153 DEGs), but not in 9–12- vs. 2–3-mo-old E3F mice. All data are from four mice per group. (G–K) SMI312⁺ neurofilaments (red) and NeuN⁺ neurons (green) in the cortex (Ctx) of 9-mo-old E3F and E4F mice (G; bar = 30 µm) and quantification of SMI-312⁺ neurites (H and I) and NeuN⁺ neuronal cell bodies (J and K) in the cortex (H and J) and hippocampus (Hipp; I and K) in 2–3-, 4–6-, and to 9–12-mo-old E4F and E3F mice. Data in H–K, mean ± SEM, n = 4–5 mice per group; significance by one-way ANOVA with Bonferroni post hoc test. *, P < 0.05; **, P < 0.01; ***, P < 0.001.