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Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury
Iliff JJ, Chen MJ, Plog BA, Zeppenfeld DM, Soltero M, Yang L, Singh I, Deane R et al.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014-12-01
Topic: Brain proteins, microglia and lab models
Traumatic brain injury (TBI) is an established risk factor for the early development of dementia, including Alzheimer's disease, and the post-traumatic brain frequently exhibits neurofibrillary tangles comprised of aggregates of the protein tau. We have recently defined a brain-wide network of paravascular channels, termed the "glymphatic" pathway, along which CSF moves into and through the brain parenchyma, facilitating the clearance of interstitial solutes, including amyloid-β, from the brain. Here we demonstrate in mice that extracellular tau is cleared from the brain along these paravascular pathways. After TBI, glymphatic pathway function was reduced by ∼60%, with this impairment persisting for at least 1 month post injury. Genetic knock-out of the gene encoding the astroglial water channel aquaporin-4, which is importantly involved in paravascular interstitial solute clearance, exacerbated glymphatic pathway dysfunction after TBI and promoted the development of neurofibrillary pathology and neurodegeneration in the post-traumatic brain. These findings suggest that chronic impairment of glymphatic pathway function after TBI may be a key factor that renders the post-traumatic brain vulnerable to tau aggregation and the onset of neurodegeneration.
Key findings
- These findings suggest that chronic impairment of glymphatic pathway function after TBI may be a key factor that renders the post-traumatic brain vulnerable to tau aggregation and the onset of neurodegeneration.
Why it matters
In mice, this study found that the brain's "glymphatic" fluid pathway helps clear tau, and that after a traumatic brain injury this pathway worked about 60% less well for at least a month. Mice lacking the water-channel protein aquaporin-4 had worse clearance after injury and developed more tau tangles and nerve-cell damage. The authors suggest this lasting drop in clearance "may be a key factor" in why injured brains become vulnerable to tau buildup, but this is animal research and tests no treatment for people.
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Study details
- Evidence strengthLow
How this study scored 55/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| Journal's citation record | 4 / 4 | Journal of Neuroscience: journal h-index 651 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2014 — within 20 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 | 7 / 7 | Cited 1,152 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 82.3 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 5 / 6 | Cited 21.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 20 other studies in this library |
| Still being cited | 4 / 4 | Cited 346 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Maiken Nedergaard: h-index 156 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Rochester: institution h-index 1,195 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25471560) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 55 / 100 | — |
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Read the original
- DOI: 10.1523/jneurosci.3020-14.2014
- PubMed: 25471560
- Original source →
- Free full text: Journal of Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Iliff, J. J., Chen, M. J., Plog, B. A., Zeppenfeld, D. M., Soltero, M., Yang, L., et al. (2014). Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.3020-14.2014
Vancouver
Iliff JJ, Chen MJ, Plog BA, Zeppenfeld DM, Soltero M, Yang L, et al. Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2014. doi:10.1523/jneurosci.3020-14.2014. PMID: 25471560.
BibTeX
@article{iliff2014-25471560,
author = {Iliff, J. J. and Chen, M. J. and Plog, B. A. and Zeppenfeld, D. M. and Soltero, M. and Yang, L. and Singh, I. and Deane, R. and others},
title = {{Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2014},
doi = {10.1523/jneurosci.3020-14.2014},
pmid = {25471560},
url = {https://doi.org/10.1523/jneurosci.3020-14.2014}
}
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