Imagine your brain cells slowly breaking down, their DNA riddled with errors, ultimately leading to a devastating condition like Chronic Traumatic Encephalopathy (CTE). It sounds like science fiction, but a groundbreaking new study suggests this may be precisely what’s happening after repeated head impacts. What if the real culprit behind CTE isn’t just the physical trauma, but a cascade of inflammation and DNA damage that silently accumulates over time?
This emerging research sheds light on the intricate connection between head injuries and CTE (you can learn more about CTE here: https://www.livescience.com/health/neuroscience/what-is-cte?utm_). The study reveals that repeated head impacts may set off a chain reaction, triggering inflammation and DNA damage within brain cells. This damage, accumulating over years, can eventually lead to cell dysfunction and, tragically, cell death. But here’s where it gets controversial… This type of damage strikingly resembles what’s observed in the brains of individuals with Alzheimer’s disease (more on Alzheimer’s here: https://www.livescience.com/65748-alzheimers-disease.html), hinting at a potentially shared mechanism of neurodegeneration.
The scientists were particularly intrigued by a previous discovery: mature neurons, cells that don’t divide, surprisingly accumulate mutations throughout life. In a 2015 study (https://hms.harvard.edu/news/natural-history-neurons), the team found that these mutations accumulate even faster in the context of brain diseases, such as Alzheimer’s. Dr. Christopher Walsh, a geneticist at Boston’s Children’s Hospital and a co-author on both the prior and new studies, explained, “We used to think neurons had the most stable genomes in the body. But it turns out, they pick up mutations year after year, and those mutations accelerate in neurodegenerative disease.” And this is the part most people miss: the implication that our brain cells are constantly evolving, and that this evolution can go awry.
This led to a crucial question: If DNA damage builds up in other brain disorders, could it also be the driving force behind the neuron loss seen in CTE? To investigate, the researchers meticulously analyzed the genomes of individual neurons from 15 deceased individuals diagnosed with CTE, along with samples from four people who had a history of repetitive head impacts but no CTE. These neurons were then compared to cells from healthy brains and those from people with Alzheimer’s disease. The team utilized single-cell whole-genome sequencing, a powerful technique that analyzes all of the DNA within each sampled cell. Think of it like taking a complete genetic fingerprint of each individual brain cell.
The results were striking. Neurons from the brains of individuals with CTE exhibited significantly more DNA mutations than those from healthy brains, averaging about 114 additional single-letter changes in the DNA code per neuron. However, neurons from individuals with a history of repeated head impacts but no CTE showed no significant increase in mutations compared to healthy brains. What does this tell us? It suggests that head impacts alone aren’t enough; there may be other factors at play that determine whether someone develops CTE.
Intriguingly, the pattern of mutations observed in CTE closely mirrored that seen in Alzheimer’s disease. Both conditions displayed an increased number of mutations and similar types of DNA alterations. As Dr. Walsh noted, their prior study revealed that “neurons, which don’t replicate, actually accumulate mutations at a steady rate throughout life. Even in healthy brains, that clock ticks forward about 17 new mutations per year from birth to old age. But in disease, that clock speeds up.” It’s like the brain’s internal clock is running wild.
Furthermore, the researchers identified another type of genetic damage: short insertions and deletions, known as indels, where letters are added or subtracted from DNA’s code. These tiny DNA breaks were more abundant in neurons from both CTE and Alzheimer’s brains compared to healthy ones. In some CTE cases, neurons contained over a thousand indels – equivalent to what might be seen in over a century of normal aging! “These indels have increased,” Walsh explained. “They’re probably numerous enough to cause serious dysfunction or death in the affected cells.” This underscores the severity and potential impact of these accumulated genetic errors.
Importantly, while this study didn’t directly measure inflammation within the neurons, previous research by study co-authors Dr. Ann McKee, a neuropathologist at Boston University (BU) CTE Center, and John Cherry, a neuroscientist at BU, has demonstrated widespread activation of microglia (the brain’s immune cells) in CTE brains. You can read more about microglia and their role here: https://pmc.ncbi.nlm.nih.gov/articles/PMC5084333/.
“We think CTE might be a combination of repeated head trauma and inflammation,” Walsh said. “That combination may bombard the genome with the same kinds of damaging processes that ultraviolet light causes in skin or tobacco smoke in the lungs,” highlighting the potential for inflammation to act as a catalyst for DNA damage. It’s a sobering analogy, comparing the effects of head trauma to the known dangers of UV radiation and smoking.
In essence, the study suggests that repeated head impacts may trigger inflammation in the brain, which, in turn, promotes the accumulation of DNA mutations in neurons, ultimately leading to cell dysfunction and death. While head trauma remains a key trigger for CTE, the long-term harm is likely driven by inflammation-driven DNA damage. This understanding could pave the way for new preventative and therapeutic strategies targeting inflammation and DNA repair mechanisms.
The team is now expanding their research to investigate whether similar processes occur in other neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) (learn more here: https://www.livescience.com/health/genetics/some-people-recover-from-als-now-we-might-know-why) and Huntington’s disease (more on Huntington’s disease here: https://www.livescience.com/health/neuroscience/trigger-for-deadly-neurodegenerative-disorder-identified). “This could be a common final pathway across diseases,” Walsh said. “We’d like to trace the biochemical steps from inflammation to neuron death and figure out where we can intervene.” This ambitious goal could revolutionize our understanding and treatment of a wide range of devastating neurological conditions.
This research raises some profound questions: If inflammation is a key driver of CTE, could anti-inflammatory interventions help prevent or slow the progression of the disease? Could we develop therapies that specifically target DNA repair mechanisms in neurons? And perhaps most importantly, what responsibility do we have to protect athletes and others at risk of repeated head impacts? What are your thoughts? Do you agree with the researchers’ conclusions? Let us know in the comments below!