Tau Processing by Mural Cells in Traumatic Brain Injury and Alzheimer's Disease
Technical Report,30 Sep 2016,29 Dec 2019
Roskamp Institute Sarasota United States
Pagination or Media Count:
One of the pathways responsible for the removal of solutes from the brain involves brain vascular mural cells. Previously, we found that mural cells associate with tau which accumulates in the brain following traumatic brain injury, TBI to a greater extent than other cerebrovascular cells. The purpose of the current proposal is to investigate mural cell status following repetitive mild TBI r-mTBI and determine the contribution of these cells to the tau pathology associated with head trauma. Consistent with other neurodegenerative disorders such as Alzheimers disease AD, we observed a progressive decline in cerebrovascular mural cell expression following r-mTBI in mice and in human TBI brain specimens. Moreover, isolated cerebrovasculature from r-mTBI and AD animals were less able to internalize tau than their respective controls. Taken together, we observed a correlation between mural cell disruption and tau processing in TBI and AD. To our knowledge, these are the first studies to observe perturbations in mural cell expression and functional tau processing in the context of brain trauma. In totality, our studies indicate mural cell disruption in TBI and AD may be an important factor in tau pathogenesis and neurodegeneration and could explain the association between head trauma and the development of AD.
- Medicine and Medical Research