Blood Vessel Changes in Tauopathy

Principal Investigator

Co-Principal Investigator

Summary

We have observed that tau, a key player in Alzheimer’s disease (AD), leads to blood vessel changes and increased expression of proteins involved in new blood vessel growth in the brains of mice. We do not know if these changes contribute to cell death and accumulation of AD proteins. This research aims to determine if blood vessel alterations are an early or late event in the disease process and to use “off the shelf” drugs to prevent blood vessel growth. Altogether, these studies will determine if the observed changes are harmful and may point towards widely available treatment options that should be considered for Alzheimer’s disease patients.

Detailed Non-Technical Summary

Our research goals are twofold 1) determine if these tau-induced vascular changes contribute to cell death and further pathological accumulation of tau and 2) test whether therapeutic interventions to prevent blood vessel changes can alter the disease course.

To achieve these goals, our laboratory is using two well-characterized mouse models of Alzheimer's disease in addition to cutting-edge microscopy techniques for visualizing alterations to vasculature in the intact, living brain.  Initial studies are aimed at understanding when blood vessel alterations occur and how changes relate to Alzheimer's disease pathology.  We are also profiling the expression of proteins involved in blood vessel growth to identify potential new targets for therapeutics.  Based on this new understanding of the relationship between tau and blood vessels, we aim to use "off the shelf" drugs to alter blood vessel growth and directly assess their effect on pathological outcomes in these models.

These studies are unique in that they examine a novel and previously unexplored interaction between tau pathology and blood vessels. Altogether, this research will determine if the observed blood vessel changes are harmful and may point towards widely-available therapeutic options to treat Alzheimer’s disease patients.

Publications

Bennett RE, Robbins AB, Hu M, Cao X, Betensky RA, Clark T, Das S, Hyman BT. Tau induces blood vessel abnormalities and angiogenesis-related gene expression in P301L transgenic mice and human Alzheimer's disease. Proc Natl Acad Sci U S A. 2018 Jan 22. pii: 201710329. doi: 10.1073/pnas.1710329115. [Epub ahead of print] PubMed Icon Google Scholar Icon
 

First published on: July 19, 2016

Last modified on: July 01, 2022