An experiment in model brains has added more evidence to the hypothesis that the viruses responsible for chickenpox and herpes can combine to cause Alzheimer’s disease.
While the claim continues to be hotly debated, researchers at Tufts University and the University of Oxford argue that they have just demonstrated that the presence of two viruses at the same time can induce an excess of proteins responsible for the characteristic plaques in the Alzheimer’s brain.
A possible link between the cold virus, herpes simplex (HSV-1) and Alzheimer’s has already received attention over the years. Not only has its DNA been found in high amounts in the brains of older people, those who have a gene linked to Alzheimer’s may have an increased risk of developing the condition if they also have HSV-1.
Similar to the herpes virus, the varicella-zoster virus can lie dormant in nerve cells for years, emerging later in life to wreak havoc as herpes.
It’s possible that the resulting inflammation could increase the risk of dementia, but herpes rarely flares up more than once or twice in a lifetime. It was unlikely, it was thought, to cause Alzheimer’s.
However, there are good reasons to suspect that the two conditions are somehow related. Population studies in Taiwan, the UK, South Korea and the US suggest that vaccination against varicella-zoster virus reemergence as herpes zoster lowers the risk of dementia, for example.
To get a better idea of what might be happening, the researchers built a brain-like environment inside six-millimeter-wide, donut-shaped sponges made of silk protein and collagen. These were populated with stem cells that grew into functional neurons and supporting tissues called glial cells, which helped keep the neurons alive and well.
When model brain tissue was infected with varicella-zoster alone, there were no signs of increased Alzheimer’s tau and amyloid beta proteins.
But if the neurons already contained a dormant herpes simplex virus, exposure to the varicella-zoster virus led to a reactivation of the herpes virus.
This double whammy was followed by a dramatic increase in tau and beta-amyloid proteins associated with Alzheimer’s disease, as well as a slowdown in neuronal signaling.
“It’s a one-two punch of two viruses that are very common and usually harmless, but laboratory studies suggest that if a new exposure to varicella-zoster virus awakens dormant herpes simplex virus, they can cause trouble,” the author says. main. biomedical engineer Dana Cairns of Tufts University.
Beta-amyloid proteins can accumulate in the brain as plaques, which are abnormal clusters of protein fragments that disrupt nerve signaling. Tau is a protein that normally keeps microtubules in straight lines. In people with dementia, tau becomes misaligned and microtubules begin to twist and tangle, killing cells of nutrients.
How these two proteins might be involved in Alzheimer’s is itself a matter of ongoing debate, with drugs that target plaque formation failing to live up to expectations. However, the fact that they are a feature of the condition makes them a clear signal that something has gone wrong.
Some experts not involved in the study have cautioned that the experiment does not definitively demonstrate that this interaction is what causes Alzheimer’s disease, because building brain-like tissue outside the human body is a highly artificial environment.
They argue that it is inflammation, a byproduct of viral infection, not the specific virus itself that is causing the problem, so other viruses may be equally implicated in the disease.
“These are laboratory findings and do not directly implicate these viruses as the main cause of Alzheimer’s disease, but the results are important and should continue to stimulate research,” says Paresh Malhotra, a neurologist at Imperial College London.
Future studies will almost certainly reveal the roles that viruses play in the complex series of events that lead to the degeneration of nerves responsible for Alzheimer’s symptoms.
“We know there is a correlation between HSV-1 and Alzheimer’s disease, and some have suggested the involvement of the varicella-zoster virus, but what we didn’t know is the sequence of events that viruses create to set the disease in motion,” he says. biomedical engineer David Kaplan at Tufts University and senior author on the paper.
“We think we now have evidence of those events.”
This paper was published in the Journal of Alzheimer’s Disease.