Effects of Mediterranean vs. Western Diets on the Cerebral Cortical Pre‐Synaptic Proteome in Nonhuman Primates

Background Western and Mediterranean diets differentially affect cerebral cortical gene expression, brain structure, and socioemotional behavior in middle‐aged female nonhuman primates (NHP) (Macaca fascicularis). In this study, we investigate the effect of diet on brain molecular composition. Method Using a machine learning approach, we quantified the impact of these diets on the presynaptic proteome in the lateral temporal cortex determined by synaptometry by time of flight (SynTOF) mass spectrometry and examined associations between the proteome, transcriptome, and an array of multisystem phenotypes. For this, we consider NHP fed with Mediterranean (n = 17) or Western (n = 19) diet for 31 months before brain retrieval (see study overview in Figure 1). Result Diet has a significant effect on presynaptic proteins (AUC = 0.86, Pvalue = 0.0002) (Figure 2A). We identified six presynaptic proteins (DAT, Aβ42, calreticulin, LC3B, K48‐Ubiquitin, SLC6A8) elevated in the presynaptic proteome bythe Mediterranean compared to the Western diet (p