Frontotemporal dementia (FTD) – what is it and how close is a cure?

You may have heard of Alzheimer’s disease, the most common cause of dementia. Around six in every 10 people with dementia have Alzheimer’s – a biological disease which damages brain cells over time.

Recently, new treatments for Alzheimer’s have made it through clinical trials, slowing memory and thinking decline in people in the earlier stages of the disease. Though the journey to curing Alzheimer’s is far from over, we have reached a historic milestone in the search for new treatments.

But what about rarer types of dementia, like frontotemporal dementia (FTD)?

We might hear far less about FTD in the news, but this condition still affects many people around the world. But what exactly is FTD? How is it different to other diseases that cause dementia, like Alzheimer’s? And how is research into it progressing?

As part of this year’s Frontotemporal Dementia Awareness events, we asked our experts to answer key questions about this less common form of dementia. Alzheimer’s Research UK’s Science Communications Manager, Jess Tobin, and Dr Teresa Niccoli, an Alzheimer’s Research UK Senior Research Fellow based at University College London (UCL), explain what research has revealed so far about the condition.

What is FTD?

Jess: FTD is a less common type of dementia, and accounts for around 1 in 30 cases of dementia in the UK. That equates, very roughly, to about 31,000 people in the UK living with FTD, although hard data is difficult to find on this. FTD affects the areas of the brain important in speech, behaviour, emotions and personality. The diseases that cause FTD lead to deterioration in these parts of the brain. This is why people with FTD may have difficulties in speaking, as well as other symptoms like changes in personality or behaviour.

Teresa: It’s called FTD because it affects areas at the front and sides of the brain of the brain, known as the frontal and temporal lobes.

Jess: People‘s experience of FTD can be very different. For example, some people have more trouble with speaking and processing language, and others show more changes in their behaviour. Doctors describe different ‘variants’ of FTD to reflect this.

Teresa: Scientists and doctors sometimes refer to FTD as a ‘spectrum’ of conditions. This is because there are many different types, which can be caused by different underlying biological mechanisms. Some of these are like other conditions affecting the brain.

What are the different variants of FTD?

Jess: The first symptoms of FTD people experience depends on where in the brain the disease processes behind FTD start. The different variants of FTD include:

• Behavioural variant FTD (bvFTD), where people’s emotions, mood or behaviour change significantly.
• Semantic dementia (the word ‘semantic’ means the meaning of language). People might forget what words mean or struggle with everyday concepts.
• Progressive non-fluent aphasia – aphasia is where people have problems speaking and writing.
• Frontotemporal dementia associated with motor neurone disease (MND). When the proteins that cause FTD build up in nerve cells involved in movement, it can lead to MND. In people with both FTD and MND (FTD-MND), the symptoms of both conditions might progress faster, but it varies from person to person.

Our dementia information pages explore the range of FTD symptoms and variants of the condition in more detail.

When does FTD usually develop?

Jess: On average, FTD tends to develop in people at a younger age compared to, say, Alzheimer’s. People diagnosed with FTD tend to be between 45 and 64, although people younger or older than this can still be affected – sometimes as young as 40.

Back in 2021, our supporter John Hirst shared his story in a blog, ‘Eight Phases of FTD’. John recalls how his wife, Pat, first started experiencing symptoms of FTD when she was around 54 years old, although it would be several years before her diagnosis was confirmed.

FTD is the most common type of ‘young-onset’ dementia, where the condition develops before a person turns 65 years old.

So, what causes FTD?

Teresa: In FTD, changes happen in nerve cells in the brain. These nerve cells send messages throughout our brain and all parts of our body. They are needed to form every thought, action, and memory we have.

In FTD, nerve cells become damaged by the build-up of particular types of protein. Our cells contain thousands of different types of protein – they’re the cell’s ‘building blocks’ and normally have vital roles in keeping our cells alive and working. But in FTD, particular proteins start to clump together inside certain groups of nerve cells. As the proteins pile up, these nerve cells can no longer work properly and start to die. This loss of nerve cells, in areas of the brain involved in language, emotions and behaviour, is what is behind the symptoms of FTD.

Sadly, as more and more nerve cells are lost, the brain as a whole can no longer function, which is why people eventually die from the diseases that cause FTD.

We don’t fully understand what triggers these proteins to start building up, but we know that there are genetic mutations that are linked to certain proteins becoming faulty, and this can lead to them clumping together. So, an urgent question for researchers is to find out what kick-starts this process, so we can find a way to stop it.

What are these proteins and what do they do?

Jess: Three proteins that build up in FTD are called tau, TDP-43 and FUS – and there are others caused by a genetic mutation in a gene called C9orf72.

Tau is a protein that’s inside nerve cells and helps to support the ‘scaffolding’ that keep a nerve cell’s shape. But in people with FTD, faulty processes in nerve cells causes the tau protein to change shape – this means it is easier for it to form clumps, called ‘tangles’, which ultimately damages nerve cells. Tau tangles can also appear in Alzheimer’s disease, the most common cause of dementia. You can find out more about tau in our fact sheet here.

Teresa: A lot of research currently focusses on how these tau tangles start to form, and then spread throughout the frontal and temporal lobes to cause FTD. The mechanisms behind this are complex and not yet fully understood, but research is helping to identify why this happens.

Jess: TDP-43 is a different type of protein to tau and is important for the cell to carry out its basic functions. But like tau, TDP-43 can also form clumps in nerve cells so they don’t work properly. Similarly, in other people, FUS proteins pile up in their nerve cells, eventually causing them to die.

Teresa: Some people with FTD have a small change, or mutation in one of their genes (genes provide ‘instructions’ to tell a cell how to make a particular protein) called C9orf72. In these people’s nerve cells, the mutated C9orf72 gene causes unusual proteins to form which eventually stops the cell from functioning.

Jess: In one of our recent Lab Notes public webinars, ‘Spotlight on frontotemporal dementia’, PhD student Benedikt Holbling explained the effects of the C9orf72 mutation in more detail. He likened the extra proteins it makes to a sentence with one word repeated over and over, so that it no longer makes sense.

Normal C9orf72: “Nerve cells contain vital molecules called proteins.”

Mutant C9orf72 (FTD): “Nerve cells contain vital vital vital vital vital vital vital vital vital molecules called proteins.”

The extra-repetitive proteins made by the mutation eventually cause nerve cells in the brain to die.

Is FTD always genetic?

Jess: Not always. In fact, only around three in every 10 people with FTD directly inherit it from their parents. In these cases, there is often a family history and it is known as familial FTD.

But there are also other, more common genetic variants that slightly increase a person’s likelihood of developing FTD, so everyone has a slightly different risk.

Researchers have looked at whether lifestyle and environmental factors – such as our heart health, level of education and air quality – can also play a role in FTD. But while these are important in determining our risk of getting dementia overall, we do not yet know how these factors affect risk of developing frontotemporal dementia specifically.

Experts do agree that taking steps such as doing regular exercise and eating a balanced diet, are generally a good idea for keeping our bodies healthy, which could in turn help keep our brains healthier for longer.

You can find out more about risk factors for dementia by using our Think Brain Health Check-in.

Are there any treatments?

Teresa: Sadly, there are currently no approved treatments available that can slow, stop or cure the diseases that cause FTD. There are potential upcoming FTD treatments in clinical trials – where experimental drugs are tested in humans to see if they works and are safe – but compared to Alzheimer’s, there are relatively few clinical trials for FTD in their later stages. Because it’s relatively rare – compared to, say, Alzheimer’s – it is more of a challenge to find new treatments because we don’t know as much about it. That’s why we urgently need more research into FTD, so that we can understand the complexities of this heart-breaking condition and use this information to identify how we can treat it.

How is research helping the search for new FTD treatments?

Teresa: In my lab, we’re interested in the way the brain processes sugar and whether modifying this could help slow the damage caused by FTD.  While investigating this process in fruit flies, we found a way to help flies with the C9orf72 mutation live for longer. It’s early days, but the work we’re doing suggests there might be ways to limit the damage caused by this mutation. If this also works in humans, it could be the basis of searching for new FTD treatments.

Jess: Alzheimer’s Research UK are proud to be funding studies like Teresa’s, which are giving us crucial insight into how we might be able to treat FTD in the future. We might be a way off yet, but it’s fundamental research like Teresa’s which is so crucial to finding a future cure.

We also fund a number of other projects related to FTD, such as identifying how certain genetic mutations lead to the condition. In combination, we hope these projects will eventually allow us to detect FTD earlier, better understand its risk factors and ultimately find a cure.

Where can I find out more information?

Jess: Our dementia information pages explain more about FTD, giving an overview of what the condition is, symptoms and how you can access more support. If you have any questions, our Dementia Research Infoline is here to help – you can contact them by phone on 0300 111 5 111, or by emailing infoline@alzheimersresearchuk.org.

You can also catch up on our Lab Notes event, ‘Spotlight on frontotemporal dementia’, where we chat to PhD student Benedikt Holbling and Prof James Rowe about their work on FTD.

• Find more information on frontotemporal dementia – Frontotemporal dementia
• Watch our Lab Notes public webinar – ‘Spotlight on frontotemporal dementia’
• Read more about Dr Teresa Niccoli’s research – What has research revealed about frontotemporal dementia?