Untangling tau in the brain

This morning we heard fascinating talks from researchers working hard to understand more about the protein tau and its role in dementia. Tau normally acts as a molecular scaffold inside nerve cells, helping them to maintain order and structure and transport cargo along their long processes. In several forms of dementia, including Alzheimer’s, frontotemporal dementia, corticobasal degeneration and progressive supranuclear palsy, tau starts to behave out of character. These changes cause it to clump together to form tau tangles inside nerve cells. The appearance of tau tangles in the brain coincides with the onset of symptoms in diseases like Alzheimer’s and so researchers believe it may be the final step in the toxic chain of events that causes nerve cells to die.

Important questions on the agenda at the Alzheimer’s Research UK Conference 2015 today were:

• how does tau damages nerve cells?
• how does abnormal tau pass its toxic signals from cell to cell?

If we can find answers to these questions, it will open doors to new approaches to treating diseases involving this culprit protein.

Communication breakdown

Diseases like Alzheimer’s and frontotemporal dementia are the result of physical changes in the brain, particularly the breakdown of communication points called synapses between nerve cells. It’s the loss of communication between nerve cells that causes the devastating symptoms of dementia like memory loss and personality change.

Dr Tara Spires-Jones, an Alzheimer’s Research UK-funded scientist from the University of Edinburgh told the full room of scientists about her work revealing that tau appears to damage synapses in the brain, putting a block on the communication that allows vital signals to pass from cell to cell. She’s recently identified a molecular chain of events that appears to play a role in executing tau’s toxic signals inside synapses, taking us closer to identifying processes to feed into the drug discovery process. Watch Dr Spires-Jones talk more about her research:

But it isn’t only nerve cells that could influence tau’s toxic effects. Cambridge-based researcher Prof Maria Grazia Spillantini revealed that other aspects of the brain environment are also affected by tau. She told the conference that the protein is affected by brain support cells called ‘glia’, as well as the environment surrounding nerve cells. She’s investigating whether targeting these interactions could provide a fruitful avenue in the search for new treatments.

Tracking tau from cell to cell

One feature of diseases like Alzheimer’s is that damage often appears to start in particular areas of the brain and then spread from cell to cell. Finding ways to stop this spread could help to protect healthy nerve cells for longer and slow or stop the progression of the disease and the worsening of symptoms.

We heard from Prof Karen Duff from Columbia University Medical Centre, who had flown in from the US to share her latest work.  She’s been studying this spread of tau across the brain in mice bred to develop the build-up of the protein seen in Alzheimer’s disease as well as in stem cells from people with dementia – done in partnership with Dr Selina Wray at UCL. Her latest work shows how abnormal tau protein can pass from cell to cell through connected brain networks. She told the audience that this transport of tau doesn’t need a physical connection, it can be passed out of one cell and taken up by its neighbour. She’s found that the more active a nerve cell is, the more it appears to be able to pass on the tau protein and investigating this link further could provide important insights into new approaches to limit this spread.

This important topic was also discussed by Dr Amy Pooler, who recently completed a Research Fellowship funded by Alzheimer’s Research UK at King’s College London. Amy emulated these findings in her own research, discovering that more active nerve cells in the laboratory were able to release more of the tau protein. We spoke about these results back in 2013 when they were first announced and since then she’s been building on the findings. She has explored ways that tau could affect the action of another hallmark Alzheimer’s protein called amyloid, finding that tau seemed to increase levels of amyloid. Her research shows a complex relationship between these two proteins that definitely need exploring in more detail. The findings from Amy’s research are already influencing research teams studying the protein around the world.

This was a lively session, as tau is a treatment target with a lot of promise. Research into tau is a key part of our Research Strategy as a charity and we’ll be keeping you updated on the important progress coming out of this area. It was also good to see a session made up entirely of female speakers, as we need to continue to encourage women to pursue careers in the higher levels of academic research.

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