September 4, 2019

expert reaction to study on single traumatic brain injury and protein tangles in the brain

A study, published in Science Translational Medicine, reports that ‘protein tangles’ associated with dementia have been detected in the brains of people who have suffered a head injury.

Dr James Pickett, Head of Research at Alzheimer’s Society, said:

“It’s well established that a major blow to head, for example from a road traffic incident or an assault, can increase your risk of developing dementia, but of course, this does not mean everyone with a head injury will get dementia.

“By looking at the distribution of tau tangles  – which are a hallmark of Alzheimer’s disease –  in the brains of people who have received a major head injury, the study confirmed that tangles can sometimes be increased many years after the injury. Previously, we could only look for tau in the brain after someone had died, but because of advances in imaging technology we can now see the build-up of tau during life. However, it did not offer any new insights into whether this can affect thinking and memory, or your risk of developing dementia.

“Research will beat dementia. Alzheimer’s Society is funding the PREVENT study to understand the relationship between lifestyle in mid-life and future brain health. While head injuries are something no one wants, and we should take every step to avoid them, in terms of dementia risk it’s better to focus on things you can control such as being physically active and following a good diet.”

Dr Carol Routledge, Director of Research at Alzheimer’s Research UK said:

“We know that traumatic brain injuries are associated with an increased risk of dementia, but we don’t fully understand how they could set dementia-causing processes into motion.

“In this small, early-stage study, researchers used sophisticated PET scans to look for brain changes in people who had sustained a TBI at least 18 years earlier. This technique revealed that people with TBI had higher levels of the tau protein in the brain compared to healthy volunteers.

“Tau is involved in multiple diseases that cause dementia and it’s crucial that we understand more about how it accumulates and spreads through the brain. It may be that this type of PET scan could help to predict which people with a TBI might go on to develop dementia, but this would have to be explored in further research.

“Understanding the long-term consequences of a head injury and the changes that lead to an increased risk of dementia, will help researchers working to find ways to protect the brain from damage.”

Prof David Curtis, Retired Consultant Psychiatrist and Honorary Professor at UCL and QMUL, said:

“I’m not really sure that this study does demonstrate that a single traumatic brain injury can lead to on-going neurodegeneration. Although the sample sizes are very small, the study does seem to show that people who had a fairly severe brain injury years ago are more likely to have MRI evidence of increased tau protein. While tau protein is involved in degenerative brain diseases I don’t think the fact that it shows up in these patients necessarily means that they are at risk of on-going neurodegeneration. It might simply be a marker of old brain injury. I don’t see evidence that it’s doing any harm in this situation. The people with higher levels of tau don’t show any clinical signs of neurodegeneration. And the tau levels aren’t any higher in the people who suffered more severe brain injuries with long-term disability.

“We don’t really know that these tau deposits are doing any harm in these patients. As the study authors state,  they are frequently found in post mortem examinations of people who have had a previous head injury. This has been known for years, so we’re not talking about a novel finding from that point of view.

“It’s useful that we can now show evidence for the presence of tau in brains of people while they are still alive. This will allow researchers to study whether areas of the brain with tau deposits are subject to neurodegeneration over time. The present study just provides a snapshot so doesn’t really allow us to draw firm conclusions.

“It is worth emphasising that this study was carried out on a small number of subjects who had suffered quite a severe head injury – bad enough to require hospital admission. And it doesn’t tell us anything new about the clinical consequences of such an injury. It reports a finding which can be visualised by a brain scan but it doesn’t say that people with this finding are any worse than those without.”

Prof John Hardy, Professor of Neuroscience, University College London (UCL), said:

“It is clear that repeated head injury can cause neurodegenerative disease with tangle pathology.  This paper appears to suggest that a single traumatic event can lead to similar build-up of tangles and this could lead to a re-evaluation of the effects of single injuries.  One very important caveat, which is clearly spelled out by the authors, is that the ligand (chemical tag) used to visualise the tangles in the living brain, is not specific and also binds to an enzyme called mono-amine oxidase.  This enzyme is also found in glial cells in the brain so a concern is that this may confound interpretation of the data.  A study of post-mortem brains is really needed to definitively answer whether this has confounded the data interpretation.”

Dr Mark Dallas, Associate Professor in Cellular Neuroscience, University of Reading, said:

“This research study highlights the fragile nature of the human brain. Using brain imaging techniques they have observed a build-up of toxic proteins, known to play a role in dementia pathology, after a single head injury event some 18 years prior. Their observations are limited by the number of brains they looked at, but certainly they show that while the initial injury is managed there may unseen (until now) consequences for brain health in the longer term. This paper builds on research looking at repetitive brain injuries, such as those experience by sportsmen and women. It should be noted that this research does not suggest that a single brain injury will automatically lead to dementia, as there are numerous other factors to consider in determining an individual’s risk of dementia.”

Prof Tara Spires-Jones, UK Dementia Research Institute Programme Lead and Deputy Director, Centre for Discovery Brain Sciences, University of Edinburgh, said:

“This study by Dr David Sharp and colleagues examined the build-up of a toxic protein called tau in the brains of people who had a single traumatic brain injury. Research over the past decades has shown robustly that people with repeated traumatic brain injury, such as professional athletes, can develop tau accumulation that is associated with cognitive problems including dementia. This study shows that a single, severe injury is associated with build-up of tau pathology detected in the brain many years after injury. The tau pathology, measured using a brain scan, was associated with worse cognitive performance and markers of brain degeneration.  While this study was conducted in a relatively small number of people (21 people who had brain injury and 11 healthy volunteers), it is important because it demonstrates that a single severe injury is likely enough to kick off lasting tau-related brain damage. These results reinforce the importance of the need for more research into how tau damages the brain so that we can eventually develop life-changing treatments for people with neurodegenerative diseases.”

‘In vivo detection of cerebral tau pathology in long-term survivors of traumatic brain injury’ by Nikos Gorgoraptis et al. was published in Science Translational Medicine at 19:00 UK time on Wednesday 4th September. 

Declared interests

Prof David Curtis: I have no conflict of interest to declare.

Prof John Hardy: John Hardy is on the SMC Advisory Committee. No declarations of interest.

Dr Mark Dallas: No interests to declare.

Prof Tara Spires-Jones: I have no conflicts of interest with this study.

None Others Received