PT  - JOURNAL ARTICLE
AU  - Iliff, Jeffrey J.
AU  - Chen, Michael J.
AU  - Plog, Benjamin A.
AU  - Zeppenfeld, Douglas M.
AU  - Soltero, Melissa
AU  - Yang, Lijun
AU  - Singh, Itender
AU  - Deane, Rashid
AU  - Nedergaard, Maiken
TI  - Impairment of Glymphatic Pathway Function Promotes Tau Pathology after Traumatic Brain Injury
AID  - 10.1523/JNEUROSCI.3020-14.2014
DP  - 2014 Dec 03
TA  - The Journal of Neuroscience
PG  - 16180--16193
VI  - 34
IP  - 49
4099  - http://www.jneurosci.org/content/34/49/16180.short
4100  - http://www.jneurosci.org/content/34/49/16180.full
SO  - J. Neurosci.2014 Dec 03; 34
AB  - 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.