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Frontotemporal dementia

Dr Laura PhippsKirsty MaraisClaire LucasRobin BrisbourneKaty StubbsEd PinchesGlyn Morris

Yesterday we heard from researchers who study frontotemporal dementia (FTD), the second most common cause of dementia in people under the age of 65. The talks focused on the biological chain of events that leads to FTD. People with FTD typically experience changes in personality, emotions and decision making; all symptoms that can be confused for other conditions. In Alzheimer’s disease, the build-up of hallmark proteins amyloid and tau in the hippocampus – the brain’s memory formation hub – leads to memory loss. In FTD there is a build-up of biological molecules in the frontal and temporal lobes of the brain. The frontal lobes regulate our personality and reasoning, so damage to the nerve cells in this region can cause a whole host of behavioural changes, from alterations in food preferences to a lack of social awareness and inappropriate behaviour. These sorts of changes are typically classed as behavioural variant FTD. Another form of FTD is called semantic dementia. In this condition, there is damage to the temporal lobes, the part of the brain involved in understanding language and communicating.

The speakers discussed the most common genetic form of FTD, caused by a mutation in the gene C9ORF72. In this form of FTD, the C9ORF72 gene is altered and a small sequence of DNA is repeated many times – like a copy and paste error in the code that makes up the gene. This repetitive sequence leads to the production of many different forms of protein, including the build-up of small strings of protein that could be toxic to nerve cells. The repeated DNA sequences also produce biological chains called RNA – a messenger molecule which acts as an intermediate step between DNA and protein. It’s these strings of protein and RNA that PhD student Alan Stepto is interested in. He uses fruit flies to understand the link between the length of the repeated DNA sequence – and so the form of protein and RNA chain produced – and behavioural changes. While using fruit flies to study a human disease might seem strange, we share a lot of our DNA with these insects. They are incredibly useful for studying the basic biological changes that occur at the beginnings of disease – something that is not possible in people. Alan found that the number of repeats affected the ability of flies to climb to different extents – an interesting insight into how biological changes in the brain are related to symptoms.

Dr Manuela Neumann also discussed these short protein strings and their build-up in the human brain. Dr Neumann uses brain tissue kindly donated by people who died with FTD to understand how changes in the C9ORF72 gene lead to nerve cell damage. Interestingly, she found that while there were lots of the short protein strings scattered around the frontal lobe of the brain, it was in fact another protein called TDP-43 that was most strongly linked with nerve cell damage and symptoms in the disease. While this suggests that TDP-43 might be more destructive than the short strings of protein that Alan studies, researchers will need to put their heads together to understand how all these different toxic proteins interact to cause symptoms and ultimately whether they can be interfered with to find a treatment. You can learn more about work going on to find treatments for FTD elsewhere on the blog.

Take a look at our Projects pages to learn more about the work we fund to understand more about frontotemporal dementia.

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