Repeated head injuries suffered by sports players and military personnel — a known risk factor for Alzheimer’s disease — may induce dementia by reactivating the dormant herpes virus in neural tissues, according to laboratory experiments.
The research at Tufts and Oxford universities, using stem cells turned to organoids or “brains in a dish”, offers more evidence that viruses, particularly those in the herpes family that are present in the majority of adults, play an important role in the development of Alzheimer’s.
The study, published on Tuesday in the journal Science Signalling, could speed up research into antiviral drugs that slow the onset of degenerative diseases.
Different experiments with brain organoids, published last week in Cell Reports by scientists at universities in the US and Israel, found that herpes infection accelerated the formation of tau, a toxic protein associated with Alzheimer’s and other neurodegenerative conditions.
Ruth Itzhaki, professorial fellow at Oxford’s Institute of Population Ageing, who worked with colleagues at Tufts, said recent studies left no doubt that viruses were involved in many cases of dementia. They are believed to harm the brain by inducing an inflammatory immune response rather than directly killing neurons.
“When I published the first evidence about viruses being active in the brain back in 1991, there was a shock-horror reaction from people in the field,” she said. “Since then evidence has appeared in more than 600 published papers but there is still quite a lot of opposition to the idea.”
According to the World Health Organization, more than 55mn people have dementia, with nearly 10mn new cases diagnosed every year. Alzheimer’s disease is the condition’s most common form, accounting for 60-70 per cent of cases.
Herpes simplex virus type-1 (HSV-1) is present in as many as 80 per cent of adults, either as an active infection or dormant, while 95 per cent harbour the relative varicella zoster virus, which causes shingles.
The Tufts and Oxford project used 6mm-wide models of the brain created from neural stem cells suffused through a spongy support, which grew into a communicating network of mature neurons.
The scientists gave the mini-brains either a single hard blow with a piston to mimic a traumatic head injury or a series of smaller jolts to mimic the effects of periodic milder concussion.
After repeated blows activated the dormant HSV-1 within the organoids, a build-up of amyloid plaque and tangles of tau protein — key markers of Alzheimer’s disease — was detected. This was not observed in uninfected organoids.
“This opens the question as to whether antiviral drugs or anti-inflammatory agents might be useful as early preventive treatments after head trauma to stop HSV-1 activation in its tracks, and lower the risk of Alzheimer’s disease,” said Dana Cairns, who led the research at Tufts.
The second study examined the molecular interactions between HSV-1 and tau proteins in brain organoids designed to model the progression of Alzheimer’s.
“Early on, changes in tau may protect brain cells by limiting the virus but, as the disease advances, these same changes could lead to more harm and accelerate neurodegeneration,” said Or Shemesh, project leader at the University of Pittsburgh and the Hebrew University of Jerusalem.
Julia Dudley, head of research strategy at the charity Alzheimer’s Research UK, said the two latest studies “offer new insights into how a common herpes virus could contribute to the early stages of Alzheimer’s disease . . . by affecting the brain’s immune system”.
She said the studies “highlight new treatment avenues, such as using medicines that target these viruses or reduce harmful inflammation in the brain”. Alzheimer’s Research UK was not involved in the studies.
According to research published last July, people vaccinated with Shingrix, which stops herpes zoster virus causing shingles, were significantly less likely to develop diseases such as Alzheimer’s.
