# Role of Cerebrovascular cells in tau processing following traumatic brain injury

> **NIH VA I01** · BAY PINES VA MEDICAL CENTER · 2020 · —

## Abstract

One of the prominent pathological features of traumatic brain injury (TBI) is the accumulation of
hyperphosphorylated and aggregated tau species in the brain. Tau is a cytoplasmic protein which is believed to
be restricted to the intracellular compartment of neurons. However, several recent studies have investigated
the existence and role for tau in the extracellular compartments of the brain, and have indicated that increased
levels of monomeric tau in the extracellular environment play a major role in the pathogenesis of
neurodegenerative tauopathies. In fact, it has been reported that extracellular tau levels in the brain correlate
with clinical outcome in TBI. Despite the prevalence and potential importance of extracellular tau in
neurodegenerative disease, there is little understanding of how extracellular tau is processed and eliminated
from the brain. Our studies demonstrate that brain vascular mural cells (pericytes and smooth muscle cells)
are involved in the processing and elimination of extracellular tau. Consistent with other neurodegenerative
disorders, we observed a progressive decline in cerebrovascular mural cell expression following repetitive mild
TBI (r-mTBI) in mice. Moreover, isolated brain vessels from r-mTBI animals were less able to internalize and
process tau than non-injured animals. To our knowledge, these are the first studies to observe perturbations in
mural cell expression and tau processing in the context of brain trauma. Importantly, alongside the mural cell
disruptions in our mouse r-mTBI model, we observed an accumulation of total tau, phosphorylated tau, and
oligomeric tau species in the brain. Additionally, we showed that tau elimination from the brain is reduced in
transgenic mural-cell depleted animals compared to wild-type mice. We propose that brain vascular mural
cells serve as a pathway for processing and eliminating tau from extracellular brain fluids and that disruption
of these cells in TBI leads to tau pathology and neurodegeneration. The objective of this project is to determine
the contribution of brain vascular mural cells to the tau pathology observed in TBI. The specific aims of this
proposal are, 1) examine mural cell status and tau pathology in mural-cell depleted animals and human TBI
brains, 2) evaluate the role of mural cells in tau degradation and elimination and the impact of r-mTBI on these
processes, and 3) determine the role of mural cells in paravascular (glymphatic) tau clearance and perivascular
tau drainage from the brain following r-mTBI. To determine mural cell status following TBI, tau uptake and
various mural cell markers will be examined in isolated cerebrovasculature from mural-cell depleted animals
and human TBI brain specimens. To understand the influence of mural cells on tau disposition, tau
degradation will be evaluated in isolated brain vasculature from r-mTBI animals and tau elimination from the
brain will be examined in mural-cell depleted animals and r-mTBI mice. Las...

## Key facts

- **NIH application ID:** 9932293
- **Project number:** 5I01BX003709-03
- **Recipient organization:** BAY PINES VA MEDICAL CENTER
- **Principal Investigator:** Corbin Bachmeier
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932293

## Citation

> US National Institutes of Health, RePORTER application 9932293, Role of Cerebrovascular cells in tau processing following traumatic brain injury (5I01BX003709-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9932293. Licensed CC0.

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