Modulating the Levels of Tau-Seed Interactors to Treat Alzheimer’s Disease

2024

This study aims to understand how the neuronal protein tau aggregates and spreads in Alzheimer’s disease (AD) and to find proteins that can stop this spread and reduce its damage to the brain. We discovered that a protein called Bassoon (BSN) interacts with tau, and when we decrease BSN, we can slow down tau spreading and improve behavior in mice with a condition similar to AD. Based on these findings, we want to study the pathological relevance of proteins that interact with toxic tau aggregates in the brains of people with AD. By analyzing data from AD patients and studying the proteins that interact with tau aggregates, we found 142 proteins linked to AD that also interact with tau. We have three main goals in our research. First, we want to see how certain proteins that interact with tau affect tau spreading and brain damage in fruit flies. Then, we will test how the downregulation of different proteins affects the formation and stability of tau aggregates in mice with AD-like conditions. Finally, we will explore if combining the downregulation of multiple proteins can further reduce the damage caused by tau in the brain. Understanding how tau aggregates exert toxicity and finding proteins that can block their harmful effects could lead to new treatments for AD. 


Funding to Date

$200,631

Focus

Studies of Tau, Translational

Researchers

Cristian Lasagna-Reeves, Ph.D.