| First Author | Iliff JJ | Year | 2014 |
| Journal | J Neurosci | Volume | 34 |
| Issue | 49 | Pages | 16180-93 |
| PubMed ID | 25471560 | Mgi Jnum | J:218748 |
| Mgi Id | MGI:5618347 | Doi | 10.1523/JNEUROSCI.3020-14.2014 |
| Citation | Iliff JJ, et al. (2014) Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury. J Neurosci 34(49):16180-93 |
| abstractText | 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-beta, 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 approximately 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. |
