Boosting tau clearance in the brain treat diseases like Alzheimer’s disease

Lead Investigator: Dr Ian Harrison

Institution: University College London

Grant type: Alzheimer's Society Dementia Research Leader Fellowship

Start date: September 2025

Duration: 60 months 

Amount: £549,996.00

Project summary

During sleep, the brain’s natural cleaning system called the glymphatic system flushes out waste, including amyloid protein, one of the hallmarks of Alzheimer’s disease.  

Dr Harrison’s previous research has shown that tau, another harmful protein that builds up inside brain cells in Alzheimer’s disease and other dementias, is also cleared away by the glymphatic system. 

However, as people age, this cleaning system becomes less effective. Dr Harrison and his team will investigate whether a new drug, TGN-073, can boost the brain’s waste removal process, helping to slow or prevent memory loss.

Project background

The hallmarks of Alzheimer’s disease are the abnormal buildup of amyloid and tau protein in the brain, leading to dementia symptoms such as memory loss and a decline in memory and thinking skills. The glymphatic system is responsible for flushing away waste products created during daily brain activity, but it functions less well as we age, potentially contributing to the progression of diseases like Alzheimer’s. 

Amyloid protein has previously been shown to be cleared by the glymphatic system. Dr Harrison’s previous work showed for the first time that tau is also removed this way. In a recent animal study, Dr Harrison found that enhancing glymphatic function with a drug targeting tiny water pores on the brain’s blood vessels reduced tau build-up and prevented memory decline. This promising work suggests that targeting this system could be a way to tackle the progression of diseases like Alzheimer’s.  Further research is needed to understand the mechanisms behind this process and turn this knowledge into an effective treatment.

What the project will involve

This project will use animal studies and advanced imaging to explore how improving the glymphatic system can help clear harmful tau proteins, one of the hallmarks of Alzheimer's disease and other dementias. It will focus on three main areas:

How improving waste clearance affects tau removal: The team will track how tau proteins build up and are cleared away in mice given a drug called TGN-073, assessing how effectively this drug improves the brain's ability to remove waste.

How the drug TGN-073 works with a key water channel (aquaporin-4): By studying mice that do not have this specific water channel protein, researchers will determine if the drug's effectiveness relies on a specific channel called aquaporin-4 and how this interaction affects the brain's waste clearance system.

The best time to start treatment: The drug will be tested during different stages of the disease to figure out when treatment works best in slowing the buildup of tau proteins and preserving memory.

Finally, the project will test if improving the brain's waste clearance can also reduce both tau and amyloid, in mice that closely mimic Alzheimer's disease in humans. This step is important to understand if the drug might also be effective in people.

How will this project help people with dementia?

In the future this research could pave the way for human clinical trials, offering hope for more effective treatments for Alzheimer’s disease and other forms of dementia.