Plasma proteome profiling of 37 individual samples both before and after exercise

Regular voluntary exercise has been shown to increase waste transport through the glymphatic system in mice. Here, we investigated the impact of physical exercise on both upstream and downstream brain waste clearance in healthy volunteers via noninvasive MR imaging. Glymphatic influx, evaluated using intravenous contrast-enhanced dynamic T1 mapping, increased significantly at the putamen after 12 weeks of chronic exercise using a cycle ergometer (P=.01). The meningeal lymphatic vessel size and flow, measured by intravenous contrast-enhanced black-blood imaging and IR-ALADDIN technique, increased significantly after chronic exercise (P=.008 and P=.002, respectively). Plasma proteomics revealed significant changes in inflammation-related and immune-related proteins (down-regulated: S100A8, S100A9, PSMA3, and DEFA1A3; up-regulated: J chain) after chronic exercise, which correlated with glymphatic influx or mLV flow (P<.05). Our results suggest that increased glymphatic and mLV flow may be the potential mechanism underlying the neuroprotective effects of exercise on cognition, highlighting the importance of long-term, regular exercise.