Fig. 6

CP2 treatment improves gene expression related to synaptic function in brain tissue of APP/PS1 mice. (a) PCA based on the RNA-seq data generated on cortico-hippocampal brain tissue shows separated clusters of samples among three groups: NTG, green; APP/PS1 (AD), blue; APP/PS1 + CP2 (AD + CP2), orange. (b–e) Heat maps show changes in genes in pathways related to dendrite morphogenesis (b), regulation of axonal extension involved in axon guidance (c), synapse assembly (d) and synaptic transmission (e) after CP2 treatment in APP/PS1 mice. (f) Western blot analysis in the hippocampal tissue demonstrates increased levels of synaptophysin (Syn), post synaptic density 95 (PSD95), brain derived neurotrophic factor (BDNF), and sirtuin 3 (Sirt3) proteins in APP/PS1 mice after CP2 treatment. (g) Quantification of the Western blot from (f) All mice were 20 months of age treated with CP2 or vehicle for 12 months, n = 4–5 mice per group for RNA-seq and n = 6–8 per group for Western blot. Data are presented as mean ± S.E.M. A one-way ANOVA with Fisher`s LSD post-hoc test was used for statistical analysis. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. The original analyses of the RNAseq data and Western blots were reported in our previous publication²⁸ and are repurposed here without major alterations.