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Long-term physical exercise facilitates putative glymphatic and meningeal lymphatic vessel flow in humans
Yoo RE, Kim JH, Moon HY, Park JY, Cheon S, Shin HS, Han D, Kim Y, Park SH, Choi SH. Nature Communications, 2025-04-09
Topic: Brain proteins, microglia and lab models
Regular voluntary exercise has been shown to increase waste transport through the glymphatic system in mice. Here, we investigate the impact of physical exercise on both upstream and downstream brain waste clearance in healthy volunteers via noninvasive MR imaging. Putative glymphatic influx, evaluated using intravenous contrast-enhanced dynamic T1 mapping, increases significantly at the putamen after 12 weeks of long-term exercise using a cycle ergometer. The putative meningeal lymphatic vessel size and flow, measured by intravenous contrast-enhanced black-blood imaging and IR-ALADDIN technique, increase significantly after long-term exercise. Plasma proteomics reveals significant changes in inflammation-related and immune-related proteins (down-regulated: S100A8, S100A9, PSMA3, and DEFA1A3; up-regulated: J chain) after long-term exercise, which correlate with putative glymphatic influx or mLV flow. 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.
Key findings
- Putative glymphatic influx, evaluated using intravenous contrast-enhanced dynamic T1 mapping, increases significantly at the putamen after 12 weeks of long-term exercise using a cycle ergometer.
- The putative meningeal lymphatic vessel size and flow, measured by intravenous contrast-enhanced black-blood imaging and IR-ALADDIN technique, increase significantly after long-term exercise.
- Plasma proteomics reveals significant changes in inflammation-related and immune-related proteins (down-regulated: S100A8, S100A9, PSMA3, and DEFA1A3; up-regulated: J chain) after long-term exercise, which correlate with putative glymphatic influx or mLV flow.
- 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.
Why it matters
In healthy volunteers, 12 weeks of long-term exercise increased putative glymphatic influx at the putamen and increased putative meningeal lymphatic vessel size and flow, alongside changes in inflammation- and immune-related plasma proteins. The results suggest increased glymphatic and meningeal lymphatic flow as a possible mechanism for exercise's neuroprotective effects on cognition, but this was a small imaging study in healthy volunteers and did not test whether exercise prevents Alzheimer's disease.
Study details
- Study designcohort
- Evidence strengthPreliminary
Limitations
Small sample of relatively healthy and young individuals, with inter-individual variability in exercise response; only one exercise modality was tested; and caffeine and alcohol abstinence was instructed but not monitored, so confounding cannot be excluded.
How this study scored 62/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 61 of the 98 points we could judge it on, which is 62 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature Communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 2 / 5 | Rated “preliminary” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 66 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 5 / 6 | Cited 23.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 3 / 4 | Cited 66 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Seung Hong Choi: h-index 65 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Seoul National University: institution h-index 1,053 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40204790) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 61 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 61 of the 98 points we could judge it on is 62 out of 100. |
| Total | 62 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 10 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Yoo, R. E., Kim, J. H., Moon, H. Y., Park, J. Y., Cheon, S., Shin, H. S., et al. (2025). Long-term physical exercise facilitates putative glymphatic and meningeal lymphatic vessel flow in humans. Nature Communications. https://doi.org/10.1038/s41467-025-58726-1
Vancouver
Yoo RE, Kim JH, Moon HY, Park JY, Cheon S, Shin HS, et al. Long-term physical exercise facilitates putative glymphatic and meningeal lymphatic vessel flow in humans. Nature Communications. 2025. doi:10.1038/s41467-025-58726-1. PMID: 40204790.
BibTeX
@article{yoo2025-40204790,
author = {Yoo, R. E. and Kim, J. H. and Moon, H. Y. and Park, J. Y. and Cheon, S. and Shin, H. S. and Han, D. and Kim, Y. and Park, S. H. and Choi, S. H.},
title = {{Long-term physical exercise facilitates putative glymphatic and meningeal lymphatic vessel flow in humans}},
journal = {Nature Communications},
year = {2025},
doi = {10.1038/s41467-025-58726-1},
pmid = {40204790},
url = {https://doi.org/10.1038/s41467-025-58726-1}
}
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