Tau Processing by Mural Cells in Traumatic Brain Injury and Alzheimer's Disease
Technical Report,30 Sep 2016,29 Sep 2017
Roskamp Institute Sarasota United States
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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 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, we observed a progressive decline in cerebrovascular mural cell expression following r-mTBI in mice. Moreover, isolated cerebrovasculature from r-mTBI animals were less able to internalize tau than sham animals. 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. Furthermore, mural cell expression is reduced in Alzheimers disease AD human brains and to a lesser extent in human TBI brains compared to control samples. 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