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Associations between the presynaptic proteome, determined by synaptometry by time\u2010of\u2010flight (SynTOF) mass spectrometry, adjacent cortex transcriptome, and multi\u2010system phenotypes were assessed using a machine learning approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Six presynaptic proteins (DAT, A\u03b242, calreticulin, LC3B, K48\u2010Ubiquitin, SLC6A8) were elevated in the presynaptic proteome in Mediterranean diet consumers (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.05). Transcriptomic data and multi\u2010system phenotypes significantly predicted SynTOF markers. Selected SynTOF markers were correlated with changes in white matter volumes, hepatosteatosis, and behavioral and physiological measures of psychosocial stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These observations demonstrate that diet composition drives cortical presynaptic protein composition, that transcriptional profiles strongly predict the presynaptic proteomic profile, and that presynaptic proteins were closely associated with peripheral metabolism, stress responsivity, neuroanatomy, and socio\u2010emotional behavior.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Mediterranean and Western diets differentially altered the cortical presynaptic proteome, which is strongly associated with neurodegeneration and cognitive decline.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Presynaptic proteomic markers were predicted by transcriptomic profiles in the adjacent cortex, and by multi\u2010system anatomical, physiologic, and behavioral phenotypes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The data demonstrate that brain phenotypes and brain\u2010body interactions are influenced by common dietary patterns, suggesting that improving diet quality may be an effective means to maintain brain health.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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