# Tau-induced endothelial cell impairment as a driver of microvascular dysfunction in Alzheimer's disease

> **NIH NIH F31** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $32,288

## Abstract

Project Summary/Abstract
Alzheimer’s disease is a progressive neurodegenerative disorder that causes significant individual suffering and
a major public health burden. The poorly elucidated pathophysiology of Alzheimer’s disease limits the
development of effective disease modifying therapy and, as a result, there are currently no therapeutic
interventions that halt or reverse the disease process. It is becoming clear that cerebrovascular dysfunction and
cardiovascular disease are major contributors to neurodegeneration and dementia. Cerebrovascular dysfunction
is the first and most significant abnormality that occurs in Alzheimer’s disease and may interact with other
pathological factors to drive the pathological progression of Alzheimer’s disease. The two hallmark pathologies
of Alzheimer’s disease are the extracellular β-amyloid plaques and intracellular neurofibrillary tangles composed
of tau protein. Preliminary studies show that transmissible soluble tau aggregates, a species of tau that is
implicated in the spread of tau pathology and neurodegeneration, accumulate in cerebrovascular endothelial
cells in vitro, in several mouse models of tauopathy, and in human patients diagnosed with Alzheimer’s disease
or other tauopathies. Exposure to soluble tau aggregates causes endothelial cell dysfunction in vitro.
Furthermore, mouse models of tauopathy show impaired endothelial function by middle age. The mechanism by
which soluble tau aggregates are transmitted to endothelial cells and their role in the development of
cerebrovascular dysfunction, however, are unclear. Published literature show that soluble tau aggregates spread
from neuron to neuron by binding cell surface heparan sulfate proteoglycans (HSPG). Based on these findings,
the proposed studies will test the hypothesis that soluble tau aggregate transmission to microvascular endothelial
cells is mediated by tau binding to cell surface HSPG and drives endothelial dysfunction in vitro and in vivo. Aim
1 will determine the role of tau binding to cell surface HSPG in soluble tau aggregate entry into endothelial cells
and the development of endothelial cell dysfunction in vitro. Aim 2 will determine the role of soluble tau
aggregates in the development of endothelial dysfunction in a mouse model of tauopathy by removing soluble
tau aggregates from the brain using antibody treatment. These studies will make use of the detailed specificity
of in vitro techniques and the translatability of in vivo approaches to characterize a novel element of
cerebrovascular pathology and Alzheimer’s disease pathophysiology. Completion of the studies proposed will
provide crucial knowledge about the etiological determinants of Alzheimer’s disease. This knowledge can be
used in the development of therapeutic interventions that target cerebrovascular dysfunction, the first abnormality
that occurs in Alzheimer’s disease. The completion of the studies proposed and the training activities detailed in
this application ...

## Key facts

- **NIH application ID:** 9992994
- **Project number:** 1F31AG067732-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Andy Banh
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,288
- **Award type:** 1
- **Project period:** 2020-08-15 → 2022-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992994

## Citation

> US National Institutes of Health, RePORTER application 9992994, Tau-induced endothelial cell impairment as a driver of microvascular dysfunction in Alzheimer's disease (1F31AG067732-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9992994. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*