How 2 common viruses may trigger Alzheimer's
- A new study finds that two very common viruses most people carry might interact to cause Alzheimer’s disease.
- Vaccines for one of the viruses appear to reduce the chances of developing Alzheimer’s.
- The research suggests that other common viruses may drive the development of the debilitating condition.
A study from researchers at Tufts University in Medford, Massachusetts reports that a combination of very common viruses may be a leading cause of Alzheimer’s disease (AD).
The virus responsible for chickenpox and shingles may activate a dormant herpes virus strongly associated in its active state with AD.
Varicella zoster virus (VZV) is the virus that causes varicella — or chickenpox — in childhood and can cause zoster — shingles — later in life.
Corresponding author of the study, Tufts’ Prof. David Kaplan told Medical News Today that “[m]ore than 95% of adults have experienced chickenpox during childhood and adolescence.” The virus remains in the body afterward.
Co-author Dr. Ruth Itzhaki, visiting professor at Oxford University and professor emeritus at Manchester University, told MNT that “age and the decline in the immune system with age, and immunosuppression” are factors that can reawaken VZV as shingles in an adult.
Before the new study, “VZV has been linked to AD, but the linkage was unclear, and the mechanisms not understood,” said Dr. Itzhaki.
The study found that when VZV becomes activated as shingles, it reactivates dormant herpes simplex virus type 1 (HSV-1). In 2021, Dr. Itzhaki published a study compiling a significant body of research showing an association between activated HSV-1 and AD.
HSV-1 is also extremely common, with 50% to 80% of American adults carrying the virus. While either the oral or genital form of VZV is active, it can cause painful blisters at the site of infection.
Dr. Itzhaki noted:
“What is known now is that infectious diseases, in general, confer a risk of AD, and our results explain this for shingles. We are now investigating if it is the case for some other infections. If it is, then it would explain the major risk posed by infectious diseases.”
“If we shift paradigms,” said Prof. Kaplan, “to focus efforts more on preventive strategies of treating these microbial species before they get a chance to wreak this havoc, we might have a better handle on preventing this disease.”
The study appears in The Journal of Alzheimer’s Disease.
Active HSV-1 and Alzheimer’s disease
“Thirty years of evidence by my lab, and subsequently by many others, suggests that HSV-1 is a major cause of AD, though the disease is obviously multifactorial,” Dr. Itzhaki told us.
According to Prof. Kaplan, “a range of factors has been reported to reactivate HSV-1 from the latent state, including stresses and disease states.” Dr. Itzhaki added “stress, immunosuppression, UV light, and menstruation” as possible triggers.
Dr. Tharick Pascoal, assistant professor of psychiatry and neurology at the University of Pittsburgh School of Medicine who was not involved in the study, commented on the findings.
“This study adds to the body of evidence suggesting that HSV-1 can lead to neuroinflammation, which is associated with an increased risk of developing Alzheimer’s disease,” he noted.
“Interestingly,” he added, “this study suggests that this occurs independently of amyloid and tau deposition, which may support the notion that there are independent pathways of neuroinflammation leading to AD, or that the presence of inflammation decreases brain reserve making patients more susceptible to the development of AD.”
“If the latter is true,” said Dr. Pascoal, “we can imagine that various viruses can increase the risk of AD, including COVID-19.”
The authors of the study noted that there is evidence that both HSV-1 and VZV can become activated after COVID-19.
Observing the varicella virus in action
Professor Kaplan told MNT that he feels his study “also demonstrates how a 3D tissue model can be used to elucidate such interactions and synergies in relatively rapid methods.” Much AD research uses animal models.
To test the effect of active VZV on inactive HSV-1, Prof. Kaplan and his colleagues created brain-like environments embedded in six millimeter-wide donut-shaped sponges made of silk protein and collagen.
Neural stem cells — some of which developed into functional neurons, and some of which became support brain glial cells — were delivered into the sponges.
When the researchers introduced VZV into the brain tissue, they found that, while the neurons became infected, there was no triggering of the development of AD’s characteristic amyloid plaques or tau-protein tangles. More importantly, the functionality of the neurons also remained unimpaired.
However, when they introduced VZV to neurons with dormant HSV-1 present, the HSV-1 became reactivated, there was increased amyloid and tau protein growth, and the electrical signals from the neurons began to slow down as they would in AD.
A new way to prevent Alzheimer’s?
Researchers have put much effort into the development of vaccines for HSV-1, but thus far, no successful vaccine exists. Some have suggested that mRNA vaccines may provide a more productive way forward.
Dr. Pascoal suggested there may be reason to hope, saying, “I think we learned a lot about mRNA vaccines during the COVID pandemic in a very short period.”
“I am optimistic that we will have effective mRNA-based vaccines for different targets in the coming years using the knowledge acquired with COVID-19,” he told us.
Dr. Heather M. Snyder, Alzheimer’s Association vice president of medical and scientific relations, and not involved in the study, however, expressed some caution.
“Any potential therapy needs to be evaluated in multiple, rigorous human studies. There are several ongoing studies using antivirals, including one funded by the Alzheimer’s Association through our Part the Cloud initiative,” she noted.
Meanwhile, although there is no vaccine for HSV-1, there are shingles vaccines. The idea that stopping VZV may help people avoid AD is supported by previous research, including Dr. Itzhaki’s own.
It has found that having had a shingles vaccine is indeed associated with a reduced risk of AD.
Meanwhile, Dr. Snyder said: “As we age, there are things that research suggests are beneficial for our bodies and our brains — engaging in physical activity, eating a balanced diet and keeping our brains active and engaged. Learn more about reducing the risk of cognitive decline and dementia on the Alzheimer’s Association website.”
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