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Tau Processing by Mural Cells in Traumatic Brain Injury and Alzheimer's Disease


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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 such as Alzheimers disease (AD), we observed a progressive decline in cerebrovascular mural cell expression following r-mTBI in mice. In particular, we observed significant reductions in an important mural cell ligand, PDGF-BB, post-injury. Moreover, isolated cerebrovasculature from r-mTBI animals were less able to internalize tau than r-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. 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.



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