Traumatic brain injury may steer Alzheimer’s pathology down a different path

A recent study published in Brain Communications has shed light on how traumatic brain injuries, such as those experienced in combat or accidents, might influence the development of brain changes associated with Alzheimer’s disease later in life. Researchers discovered that while traumatic brain injury did not lead to an overall increase in two key Alzheimer’s proteins in the brain, it did change where these proteins were deposited and how they interacted with each other. This suggests that head injuries could lead to unique patterns of brain aging that differ from typical Alzheimer’s disease.

Traumatic brain injury occurs when an external force impacts the head, potentially causing damage to the brain. The severity can range from mild concussions to more serious injuries involving loss of consciousness and lasting neurological problems. Dementia is a general term for a decline in mental ability severe enough to interfere with daily life. Alzheimer’s disease is the most common cause of dementia, characterized by the build-up of specific proteins in the brain: amyloid-beta and tau.

Amyloid-beta is a protein that can clump together to form plaques in the brain. These plaques are thought to disrupt communication between brain cells. Tau is another protein found inside brain cells that can become tangled. These tau tangles also interfere with normal brain function and are closely linked to the death of brain cells. Scientists have long observed that people with a history of traumatic brain injury seem to have a higher risk of developing dementia later in life.

However, the exact biological reasons for this link have remained unclear. Researchers have been investigating whether the build-up of amyloid-beta and tau, the hallmarks of Alzheimer’s disease, might be the missing link between traumatic brain injury and later dementia. Prior studies exploring this connection have produced mixed results, with some finding increased amyloid-beta and tau after brain injury, and others finding no such increase.

To gain a clearer understanding, researchers in this new study focused not just on the overall amounts of amyloid-beta and tau, but also on their specific locations in the brain after traumatic brain injury. They hypothesized that traumatic brain injuries, which can cause damage in specific areas of the brain depending on the type of injury, might lead to different patterns of amyloid-beta and tau build-up compared to the more typical patterns seen in Alzheimer’s disease.

Free daily newsletter

“The buildup of harmful proteins like amyloid-beta and tau in the brain varies across individuals, leading to different clinical profiles in neurodegenerative disorders like Alzheimer’s disease,” said study author Hannah de Bruin, a PhD student at Amsterdam University Medical Center.

“Our research focuses on understanding this variability—why these proteins accumulate and spread in distinct ways. Traumatic brain injury, which can result from events like contact sports, military service, or falls, provides a unique opportunity to study this heterogeneity. Since traumatic brain injury can affect different brain regions depending on the type of injury, they create diverse conditions that could help us better understand how protein buildup and interactions differ between individuals.”

The study included 103 male Vietnam War veterans, with an average age of about 67 years. Of these, 65 had a history of traumatic brain injury, while 38 had no history of brain injury and served as the control group. Among those who had experienced a brain injury, 40 had mild injuries and 25 had moderate-to-severe injuries. Most individuals had experienced one or two traumatic brain injuries in their lifetime. The study was conducted decades after these injuries, with an average time gap of about 40 years between the last injury and the brain scans performed for this research.

To measure amyloid-beta and tau in the brain, all participants underwent specialized brain imaging using positron emission tomography (PET) scans. These scans allowed researchers to observe where these proteins were accumulating in the brain. They then compared the distribution patterns of these proteins between individuals with and without a history of traumatic brain injury.

The researchers did not find that individuals with a history of traumatic brain injury had higher overall levels of amyloid-beta or tau compared to those without a history of brain injury. This suggests that traumatic brain injury does not necessarily lead to an increase in these harmful proteins across the entire brain. However, researchers did identify a key difference in how the proteins were distributed.

In people who had experienced traumatic brain injury, amyloid-beta and tau were more likely to be found in the frontal and parietal regions of the brain. These are areas that are particularly vulnerable to damage from traumatic brain injury. In contrast, in people without a history of traumatic brain injury, these proteins were more concentrated in the temporal region of the brain, which is where they typically accumulate in Alzheimer’s disease. This finding suggests that traumatic brain injury may alter the typical pattern of how these proteins spread over time.

Additionally, the relationship between amyloid-beta and tau appeared to be different in individuals with traumatic brain injury. In Alzheimer’s disease, amyloid-beta and tau tend to accumulate together in specific brain regions, with amyloid-beta often triggering the spread of tau. However, in individuals with a history of traumatic brain injury, this relationship was weakened in the temporal regions (which are typically the first areas affected in Alzheimer’s disease) and was instead stronger in the frontal regions. This suggests that traumatic brain injury may not only change where these proteins accumulate but also how they interact with each other.

“We found that a history of traumatic brain injury was not necessarily associated with higher overall levels of amyloid-beta and tau on PET imaging, but their distribution and relationships varied,” de Bruin told PsyPost. “Specifically, these proteins were more concentrated in brain regions typically affected by traumatic brain injury, such as the frontal and parietal lobes, rather than in the temporal regions, which are more commonly related to early Alzheimer’s disease. Additionally, amyloid-beta and tau showed stronger associations in these areas related to traumatic brain injury. This suggests that traumatic brain injury may influence both the location and dynamics of these proteins, contributing to distinct neurodegenerative trajectories.”

“As with every study, there are some important caveats to consider,” she noted. “Our sample size was relatively small (103 participants), so future research with larger groups is needed to confirm our findings. Additionally, since this was a cross-sectional study, we could not track how the relationship between traumatic brain injury and amyloid-beta and tau might develop over time.

“Another point to consider is that amyloid-beta and tau levels in our participants were generally low, so it would be valuable to examine whether the same findings hold true in a cohort with higher levels. And lastly, while PET imaging is a well-established method for visualizing amyloid-beta and tau in living individuals, post-mortem examination remains the gold standard for detecting these proteins with certainty.”

Moving forward, the researchers are interested in exploring how the brain’s communication networks, or functional connectivity, might influence the spread of tau protein in Alzheimer’s disease, particularly in the context of traumatic brain injury. Understanding these mechanisms could lead to better predictions of disease progression and potentially inform the development of more targeted treatments for individuals with a history of head injury.

“We are currently working on new projects that explore functional connectivity—essentially, how different regions of the brain communicate with each other—as a potential predictor of how tau spreads in Alzheimer’s disease,” de Bruin explained. “This is particularly important because tau is the protein most closely linked to neurodegeneration and cognitive decline. We believe that tau spreads through the brain by following the connections of the regions where it first emerges, driving how the disease biologically develops and, in turn, how it clinically manifests. The ultimate goal is that our research findings will improve predictions of disease progression and inform clinical trial designs, eventually leading to the development of more effective treatments.”

The study, “Amyloid-β and tau deposition in traumatic brain injury: a study of Vietnam War veterans,” was authored by Hannah de Bruin, Colin Groot, Suzie Kamps, Everard G B Vijverberg, Anna Steward, Amir Dehsarvi, Yolande A L Pijnenburg, Rik Ossenkoppele, and Nicolai Franzmeier for the Alzheimer’s Disease Neuroimaging Initiative (ADNI).