Understanding how tau builds up in the brain in Alzheimer’s disease

Lead Investigator: Dr Cara Croft

Institution: Queen Mary University of London

Grant type: Alzheimer's Society Dementia Research Leader Fellowship

Start date: February 2025

Duration: 60 months 

Amount: £549,747.32

Project summary:

In diseases like Alzheimer’s disease, the tau protein forms small knots inside brain cells, which grow into larger tangles. Normally, the body clears out unnecessary tau, but in people with these diseases, it builds up and harms brain cells eventually causing the cells to die and the symptoms of dementia appear. Dr Croft’s previous research shows that tau knots can unravel on their own, but very slowly.  

Dr Croft’s project will help us to understand how tau breaks down and whether we can speed up this process to prevent harmful tangles from forming. By identifying ways to boost tau removal, researchers could develop new treatments that could slow or prevent Alzheimer’s disease.

Project background: 

Alzheimer’s disease and similar brain conditions, called tauopathies, are linked to the abnormal buildup of a protein called tau. When tau builds up, it forms knots which can then develop into tangles. Dr Croft and her team developed an innovative technique to watch tau knots form in real-time in mouse brain slices. 

For the first time, they discovered that when tau protein knots have newly appeared in the brain, the body can efficiently break them down and recycle the tau. But the longer these knots remain in the brain—such as in later stages of the disease—the harder it becomes for the body to recycle them. This is important when thinking about when to give a treatment to ensure it is most effective.

This discovery suggests that the body may have ways to clear or regulate tau buildup, Dr Croft aims to understand these processes. By understanding which of the unravelling processes is most important, Dr Croft hopes to uncover new ways to prevent or slow these diseases. Understanding these natural processes could help in designing treatments to keep brain cells healthy and working properly for longer.

What does this project involve?

This project aims to figure out how the body clears tau and whether we can boost this process to treat conditions like Alzheimer’s disease. The study will focus on three key areas:

1. Understanding how the body removes tau: Using special virus-based tools, Dr Croft and her team will examine how cells break down tau through natural processes like waste removal and cell-to-cell communication. Studying these processes in detail will help identify weak points where steps can be taken to improve tau clearance and reduce its harmful effects in the brain.
2. Tracking tau in models: The team will create small, lab-grown brain tissue models to watch how tau behaves and is cleared over time. These models will allow scientists to watch tau build up and removal in real time, giving valuable insights into what factors influence tau buildup and whether certain conditions make it worse or better.
3. Exploring potential treatments: By testing different drug candidates, researchers will see if they can improve tau removal and find promising treatments. If successful, this research could lay the foundation for future clinical trials, where new treatments could be tested in people to determine if they help slow or prevent the progression of Alzheimer’s disease and related diseases.

How will this project help people with dementia?

If we can find ways to help the brain clear harmful tau more effectively, it could slow or stop the progression of diseases like Alzheimer’s disease. This could lead to new treatments in the future that improve the lives of more people living with dementia.