differences in protein expression from both neurons of the DS and presynaptic inputs arriving from other brain regions. Alternatively, proteomics is less sensitive to lowly expressed proteins (as one cannot amplify proteins similar to amplifying mRNA), and additional biological replicates for the proteomics data may have increased the number of less abundantly expressed proteins identified as significantly differentially expressed between lines which could have altered the correlation between our transcriptome and proteome results. Minimal overlap was also observed for differentially expressed proteins and phosphorylated proteins (34 identified from 390 and 345 proteins and phosphorylated proteins, respectively) which suggests that the alterations in protein phosphorylation states reflect specific protein phosphorylation changes that are not simply due to changes in global protein abundance. This represents a strength of our complimentary multi-omics approach as RNA-sequencing and global proteomics cannot detect these dynamic and rapid peptide phosphorylations differentially occurring in the DS of HAP and LAP mice which our quantitative phosphoproteomics approach captured.