Figure 5.

APOE4 effects on synaptic interactome and behavior. (A and B) PSD95 protein interactors (PSD95 interactome) determined in four replicates from the cortex. (A) Disrupted PSD95 PPI networks in 7-mo-old E4F compared with E3F mice. Affected protein interactors localized within highly connected nodes of the PPI. (B) PPIs networks in 2–3-mo-old E4F compared with E3F mice. In A and B, green, PSD95 node; gray, no detected changes in PSD95 PPI ratios; pink (A) or orange (B), impaired PSD95 PPI ratios. The PSD PPI network was constructed by immunoisolation and mass spectrometry analysis of Shank3, Syngap1, Homer1, Cyfip1, Cyfip2, Cnksr2, Nckap1, TNiK, Fmr1, Tsc1, and Dlgap1 nodes. In A and B, all measurements were performed simultaneously in four biological replicates per genotype and age. For full description of dysregulated PPI networks, see the main text and Table S1, N–P. (C–F) Novel object location (NOL; C) novel object recognition (NOR; D), nesting (E), and burrowing (F) in 4–6- and 6–8-mo-old E3F and E4F mice. Mean ± SEM. In C–F, n = 14–16 mice per group. Significance by one-way ANOVA with Bonferroni post hoc test (C–F). **, P < 0.01; ****, P < 0.0001.