“Our results suggest a pathway to Alzheimer’s disease, where VZV infection induces inflammatory agents that wake HSV in the brain,” said Dana Cairns, GBS12, a research associate in the Department of Biomedical Engineering. . “While we have demonstrated a link between VZV and HSV-1 activation, it is possible that other inflammatory phenomena in the brain may also awaken HSV-1 and lead to Alzheimer’s disease.”
The study was published in the Journal of Alzheimer’s Disease
Virus is waiting
“We have studied a lot of strong evidence that HSV is associated with an increased risk of disease,” said David Kaplan, Stern Family Professor of Engineering and chair of the Department of Biomedical Engineering at Tufts School of Engineering. Alzheimer’s in patients. One of the first to hypothesize a link between the herpes virus and Alzheimer’s disease was Ruth Itzhaki of the University of Oxford, who collaborated with the Kaplan lab on this study.
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“We know there is a correlation between HSV-1 and Alzheimer’s disease, and some have suggested an association with VZV, but what we don’t know is the sequence of events the virus produces to cause the disease,” he said. This disease is in the advanced stage. “We think we now have evidence of those events.”
According to the World Health Organization, an estimated 3.7 billion people under the age of 50 have been infected with HSV-1, the virus that causes oral herpes. In most cases, it is asymptomatic, lying dormant in the nerve cells.
When activated, it can inflame nerves and skin, causing painful sores and blisters. Most carriers — and that’s one in two Americans according to the CDC — will have symptoms that range from very mild to no symptoms before the virus goes dormant.
The varicella zoster virus is also extremely common, with about 95% of people infected before the age of 20. Many cases manifest as chickenpox. VZV, which is a form of the herpes virus, can also survive in the body, making its way to nerve cells before going into a dormant state.
Later, VZV can reactivate to cause shingles, a disease characterized by blisters and nodules on the skin that form bands and can be very painful, lasting weeks or even months. One in three people will eventually develop a case of shingles in their lifetime.
The link between HSV-1 and Alzheimer’s disease only occurs when HSV-1 has been reactivated to cause sores, blisters, and other painful inflammatory conditions.
How can a sleeping virus wake up?
To better understand the cause-and-effect relationship between the virus and Alzheimer’s disease, Tufts researchers recreated a brain-like environment in small, 6-mm-wide donut-shaped sponges made from silk proteins and collagen.
They create sponges with neural stem cells that develop and become functional neurons capable of transmitting signals to each other in a network, just as they do in the brain. Some stem cells also form glial cells, which are commonly found in the brain and help keep nerve cells alive and active.
The researchers found that neurons growing in brain tissue can become infected with VZV, but that alone does not lead to the formation of Alzheimer’s-specific proteins tau and beta-amyloid — the composition of the mess of fibers and plaques that form in Alzheimer’s disease patients’ brains — and neurons that continue to function normally.
However, if neurons that already harbor HSV-1 are inactive, exposure to VZV leads to reactivation of HSV, with significant increases in tau and beta-amyloid proteins, and signals Nerve signals begin to slow down.
“It’s a punch of two very common and often harmless viruses, but laboratory studies show that a fresh exposure to VZV wakes dormant HSV-1,” Cairns said. , they can cause trouble.
“It remains possible that other infections and other causal pathways may lead to Alzheimer’s disease, and risk factors such as head trauma, obesity or alcohol consumption suggest they may intersect when HSV recurs. appear in the brain,” she added.
The researchers observed that the samples infected with VZV began to produce higher amounts of cytokines – proteins normally involved in triggering an inflammatory response. Kaplan notes that in many clinical cases, VZV is known to cause encephalitis, which can lead to dormant HSV activation and increased inflammation.
Repeated cycles of HSV-1 activation can lead to more inflammation in the brain, production of plaques, and accumulation of neuronal and cognitive damage.
The VZV vaccine — to prevent chickenpox and shingles — has also been shown to significantly reduce the risk of dementia. It is possible that vaccines are helping to stop the cycle of virus reactivation, inflammation and nerve cell damage.
The researchers also noted the long-term neurological effects that some COVID patients experienced from the SARS-CoV-2 virus, especially in the elderly, and that both VZV and HSV-1 may be possible. reactivated after COVID infection. Monitoring for possible cognitive effects and neurodegeneration would be advisable in these cases, they said.
Source: Eurekalert
