How head trauma leads to dementia

07 August 2018

Interview with

Willie Stewart, University of Glasgow

Brain injury

Brain injury

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People who receive repeated knocks on the head, like sports players, or individuals who get head-injured in car accidents and falls, are at higher risk later in life for a form of dementia similar to Alzheimer’s Disease. Why this happens though, no one knew. But Glasgow pathologist Willie Stewart has been studying the brains of patients with a past history of head trauma. He’s found deposits of a protein called tau throughout their nervous systems. And by studying animals with similar brain injuries, it looks like the initial trauma provokes the formation of tau aggregates at the injury site, which then alarmingly promote their own formation elsewhere around the brain, spreading along nerve pathways, damaging nerve cells and triggering dementia. The good news is that now scientists know this, it might be possible to develop a way to stop it, as Chris Smith found out...

Willie - In many of the studies that have looked at people surviving brain injury they report that there is an increase in the risk of of Alzheimer's disease. But we’re also getting better at recognising that in many of these cases it’s a distinct form of dementia different to Alzheimer's disease and it’s one that we call Chronic Traumatic Encephalopathy or CTE for short, and it used to be known as Boxer’s Dementia.

Chris - How long after the injury do you tend to see these manifestations?

Willie - Well, patients who turn up clinically with problems it’s often several decades after the injury and the problem is what’s happened in that time from when they were exposed to brain injury to the development of dementia. What we were doing in our study was looking at people with a shorter period of survival to try and get a picture of that timeframe in between.

Chris - So what did you actually do?

Willie - We did two things. Firstly, we looked at material from patients who’d survived a brain injury. On average about five years after brain injury and looked at what their brains looked like compared to normal ageing brains. And what we found in that was that they had a deposition of an abnormal protein in their brain which we then went on to look at in an animal model to see if we could replicate that and figure out what was happening in these patients.

Chris - What was the protein that you found there that shouldn’t be?

Willie - What we found was an abnormal protein in the brain, or abnormal form of a protein in the brain called Tau. Actually it’s a protein that we’d normally have in our brains to kind of hold the structure of the brain together. It’s a very important protein but sometimes, for reasons we don’t understand, that protein can become abnormally processed or abnormally folded, and it’s that abnormal protein that causes problems down the line. So that’s what we were looking for and we saw this in greater quantities in wider distribution in patients who’d had a brain injury than in normal ageing.

Chris - So when you say it’s in a wider distribution, so rather than just seeing it where their brain was worst affected, you’re saying it’s everywhere or in more places than just the primary injury site?

Willie - Again, we were looking at patients who’d survived quite some number of time after the original injury, and what we found was that tau protein was throughout their brain. In normal ageing it can just be in tiny spots here and there as part of an ageing process, but we found it was spread throughout the brain more like you might see, again, in patients with Alzheimer’s disease or CTE.

Chris - Was the buildup of the protein associated with some kind of other damage to the brain, as in, can you say that where you see that tau protein there’s also evidence that the cells are dying or the brain is changing in those areas?

Willie - Certainly we can say that that abnormal protein is toxic to the neurons in the brain and causes further problems, but also there are other things happening too. I think what we do though is take those observations in our human material, which is really important and we take that back into a stripped back animal study where we can look at specifically what’s happening to the neurons at that point.

Chris - How do you know the tau protein is there and it’s damaging the brain in that area rather than some brain was damaged in that area and it left behind some tau protein?

Willie - Well, that’s a brilliant question. And that’s really what we tried to set out to do. Because we can see this in Alzheimer’s disease, and we can see this in CTE, and we can now see it in our patients after a single brain injury that they have this abnormal tau protein. And our question was did that protein appear as a result of some other process in the brain so that other damage that the injury had done had caused the tau protein to be deposited, or is the tau protein actually the real problem?

Chris - Which do you think it is?

Willie - That’s what our research has probably uncovered here - at least part of the story. Because what we can do with the animal model is that we can create a similar injury to what our patients had - a thing you might get with a car crash, and we can follow the progression of that tau pathology over time. And what we found is that it’s that abnormal tau protein that appears to migrate through the brain and appears to infect, if you like, the rest of the brain.

Chris - So there’d be an injury which is centered on say one brain region. The injury would trigger the formation of some of this abnormal form of this tau protein and it would then propagate along the nerve pathways that the injured areas connected to and begin to deposit tau in other areas that are anatomically linked?

Willie - That’s exactly it. That’s certainly what our evidence strongly supports. Obviously, this an initial study showing very strong evidence suggesting that that’s what’s happening. Now what we need to do is start to do the really clever stuff and figure out exactly what’s happening at the cellular level. More importantly, if we can figure this one out, we might actually have a way of trying to treat patients and avoid people getting dementia in this way.

Chris - Do your findings inform how we should manage head injury better in the future?

Willie - Yeah. That’s the really exciting thing that we’re taking forward from this research is that here we have a potential target, an abnormality that develops at the time of injury that seems to be partly responsible for driving later disease. So this abnormal tau protein formed at the time of injury seems to then go on and propagate through the brain, so if we can in some way figure out a means to stop that happening potentially what we could do is prevent the dementia developing later down the line.

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