RT Journal Article
SR Electronic
T1 Impairment of Glymphatic Pathway Function Promotes Tau Pathology after Traumatic Brain Injury
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 16180
OP 16193
DO 10.1523/JNEUROSCI.3020-14.2014
VO 34
IS 49
A1 Jeffrey J. Iliff
A1 Michael J. Chen
A1 Benjamin A. Plog
A1 Douglas M. Zeppenfeld
A1 Melissa Soltero
A1 Lijun Yang
A1 Itender Singh
A1 Rashid Deane
A1 Maiken Nedergaard
YR 2014
UL http://www.jneurosci.org/content/34/49/16180.abstract
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.