A study published recently revealed new evidence linking a single traumatic brain injury (TBI) with increased dementia risk.

Scientists visualised “tangles” or clumps of the protein tau – associated with the onset of Alzheimer’s and other forms of dementia – in people who had experienced a moderate to severe TBI 18 to 35 years earlier.

The study was small and early-stage, with only 21 brain injury cases and 11 healthy individuals studied.

But the findings made headlines, with results providing further evidence that a single TBI could lead to brain damage decades later, despite individuals seemingly completing a full recovery in the aftermath of the trauma.

Tau tangles have been detected in the brains of patients in post-mortem examination – where findings suggest around one in three patients with a single head injury develop them.

Most commonly, they have been recorded in brains donated for studies into the impact of repeated blows in boxing, football and American football; largely through research into chronic traumatic encephalopathy (CTE) and its implication in neurodegeneration in later life.

This was the first time, however, that scientists had captured them in living patients following a single blow to the head, using a new ‘positron emission tomography’ (PET) imaging technique.

The findings showed that the TBI survivors were more likely to have tau tangles than members of a healthy group.

The research involved scientists at Imperial College London’s (ICL) Dementia Research Institute and the University of Glasgow and was published in Science Translational Medicine.

Dr Nikos Gorgoraptis, the author of the paper, from ICL’s brain sciences department, said: “Scientists increasingly realise that head injuries have a lasting legacy in the brain and can continue to cause damage decades after the initial injury.

“However, up until now most of the research has focussed on the people who have sustained multiple head injuries, such as boxers and American football players.

“This is the first time we have seen these protein tangles in patients who have sustained a single head injury.”

The study used a PET brain scan combined with a substance that binds to tau protein, called flortaucipir, to study the amount of tau protein in the brains of head injury patients.

While patients with head injury were found to be more likely to have tau tangles, the paper also showed that patients with tau tangles had higher levels of nerve damage, particularly in the white matter of the brain.

None of the healthy individuals had tau tangles. Also, patients with higher levels of tau tangles did not necessarily have any reduction in brain function, such as memory problems, compared to patients with fewer tangles.

However, Dr Gorgoraptis adds that these tangles can develop years before a person starts to develop symptoms such as memory loss.

He explained there are still many questions to answer about the tau tangles and brain damage. He also believes the findings could lead to the development of new treatments.

“This research adds a further piece in the puzzle of head injury and the risk of neurodegeneration,” he said.

“Not all patients with head injury develop these protein tangles, and some patients can have them for many years without developing symptoms.

While we know tau tangles are associated with Alzheimer’s and other forms of dementia, we are only beginning to understand how brain trauma might lead to their formation.

“What is exciting about this study is that this is the first step towards a scan that can give a clear indication of how much tau is in the brain, and where it is located.

“As treatments develop over the coming years that might target tau tangles, these scans will help doctors select the patients who may benefit and monitor the effectiveness of these treatments.”

Science’s understanding of tau tangles has accelerated in recent years as laboratories lead the fight against the world’s dementia crisis.

Earlier this year, researchers at Ohio State University in Columbus devised a mathematical model to help explain the biological processes behind the formation and growth of tau tangles.

They started with a basic two-step model of tau aggregation; two tau proteins slowly bind together, then additional tau molecules attach themselves to the two proteins.

However, after studying tau tangles under a microscope, they also discovered another process which speeds their growth.

They found that short fibrils of the tau protein can attach themselves to each other to form longer ones, elongating a fibril more quickly.

Study co-author Jeff Kuret explained that “once a long fibril is broken up into little pieces, they can diffuse, facilitating their movement from cell to cell”.

The researchers now plan to further develop their model to account for the many complexities of the tau protein.

There are six isoforms of the protein, yet this study only used one, while various chemical processes, including phosphorylation, can further change the structure of the protein.

Another study breaking new ground on our understanding of tau tangles was published in August.

The research into brain samples of confirmed CTE cases among former American footballers, found correlation between the formulation of tau tangles and the number of years the individual played the sport.

Lead author Michael Alosco, of Boston University, found that years of football play correlated with tau tangle burden in the dorsolateral prefrontal cortex, a region known to shoulder early and severe burden of tau pathology in people with CTE.

Men who played longer also had more severe white-matter rarefaction, a combination of white-matter loss and gliosis (a change of glial cells following central nervous system damage).

Tau burden and white- matter pathology each contributed similarly, and independently, to the chances of a dementia diagnosis.

People with moderate to severe levels of white-matter loss or tau pathology had 1.69 and 2.65 times the odds of dementia, respectively, of their counterparts with mild amounts either pathology.