Researchers from Oxford’s Institute of Population Ageing and the University of Manchester, and Tufts University have found that head injuries, such as those induced in sports and the military, may re-awaken dormant viruses in the brain, triggering the onset of conditions including Alzheimer’s Disease and dementia.
The new study suggests that repeated head injuries, such as concussions, a known risk factor for Alzheimer’s disease (AD), may reactivate a common dormant virus in the brain, increasing the risk of AD and other neurodegenerative conditions. Researchers found that even mild brain trauma can trigger this chain reaction, leading to harmful changes associated with memory loss and cognitive decline.
In previous studies, the researchers demonstrated the roles that common viruses, such as herpes simplex virus type 1 (HSV-1) (the so-called cold sore virus) and varicella zoster virus (VZV) (which causes chickenpox and shingles) play in the development of AD. HSV-1 can lie dormant in human cells for a lifetime, but when it re-awakens it can cause changes that resemble changes observed in AD patients’ brains – amyloid plaque-like formations (PLFs), gliosis, neuroinflammation, and decreased functionality.
In the latest study, published today in Science Signaling, the researchers once again used their small, 3D, bioengineered human brain tissue model to test the effects of physical trauma on the brain cells. When the brain tissues were exposed to repeated “mild blows,” similar to concussions, the previously dormant HSV-1 virus became active. This reactivation triggered inflammation, beta-amyloid plaque build-up, and the formation of harmful tau proteins, which can damage brain cells and impair memory.
Importantly, the researchers also found that blocking an inflammatory molecule called Interleukin-1 beta (IL-1β) prevented many of these harmful effects in lab models, opening the door to potential new treatments for those at risk.
Professor Ruth Itzhaki, who led the research with Drs Cairns and Kaplan at Tufts, has been researching the potential role of HSV-1 in AD for more than 30 years, beginning at the University of Manchester, where her team discovered HSV-1 DNA is present in the human brain in a high proportion of older people – the first microbe to be detected definitively in normal human brains.
Professor Itzhaki, Visiting Professorial Fellow at the Oxford Institute of Population Ageing and Emeritus Professor at the University of Manchester, said: “Head injuries are already recognised as a major risk factor, as are the cumulative effect of common infections, for conditions such as Alzheimer’s and dementia, but this is the first time we have been able to demonstrate a mechanism for that process.
“What we’ve discovered is that in the brain model these injuries can reactivate a dormant virus, HSV1, setting off inflammation which, in the brain, would lead to the very changes we see in Alzheimer’s patients.
“Understanding both the risk factors for dementia and Alzheimer’s, and the mechanism by which they develop, is important in being able to target treatment and prevention at as early a point as possible.”
The researchers hope their work will pave the way for new treatments to protect against neurodegeneration, particularly for those at high risk due to repeated concussions.
The full paper, ‘Repetitive injury induces phenotypes associated with Alzheimer’s disease by reactivating HSV-1 in a human brain tissue model’, is published in Science Signaling.
