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Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation  jcm9144@gmail.com

SPECIAL REPORT #22.11

A Link between Reactivation of the Herpes Virus HSV-1 and Alzheimer’s disease?

Published by Megan Brooks from Medscape

August 19, 2022

Varicella zoster virus (VZV) infection, by reactivating dormant herpes simplex virus (HSV-1), is thought to lead to neuroinflammation and the accumulation of Alzheimer's disease (AD)-related proteins in the brain, according to a new study. "Our results suggest a [possible new cause] of Alzheimer's disease induced by VZV infection that creates inflammatory triggers that awaken HSV in the brain," said lead author Prof. Dana Cairns, department of biomedical engineering at Tufts University, Boston, in a press release.

The findings were published online Aug. 2 in the Journal of Alzheimer's Disease.

Previous research has suggested a correlation between HSV-1 and AD and the involvement of VZV. However, the sequence of events that triggered the disease was unclear.

"We believe we now have evidence of this cascade of events," said co-senior author David Kaplan, PhD, chair of the Department of Biomedical Engineering at Tufts, in the release.

In collaboration with co-senior author Ruth Itzhaki, PhD, of the University of Oxford, UK, the researchers infected human neural stem cells (hiNSCs) and 3D brain tissue models with HSV-1 and/or VZV.

The researchers found that infection of hiNSCs with HSV-1 induced accumulation of beta-amyloid and P-tau, respectively the major components of Alzheimer's disease plaques and neurofibrillary tangles. In contrast, VZV infection of cultured hiNSCs did not result in beta-amyloid and P-tau accumulation, but rather in gliosis and increased levels of pro-inflammatory cytokines. "Strikingly, VZV infection of quiescent HSV-1-infected cells caused HSV-1 reactivation, resulting in AD-like changes, including accumulation of beta-amyloid and P-tau," the researchers report.

This suggests that VZV is probably not a direct cause of AD, but rather acts indirectly via HSV-1 reactivation, they add. Similar results have appeared in similar experiments using 3D human brain tissue models. "This is a combination of two very common and generally harmless viruses, but laboratory studies suggest that if re-exposure to VZV wakes up the dormant HSV-1, they could cause problems," Cairns said. The researchers note that VZV vaccination has already been shown to reduce the risk of dementia. It's possible, they add, that the vaccine helps stop the cycle of viral reactivation, inflammation and neuronal damage.

Speaking to Medscape Medical News, Dr. Heather M. Snyder, vice president of medical and scientific relations for the Alzheimer's Association, said that "while this is a first step, it could provide valuable guidance for further research. This is preliminary work that first needs to be replicated, validated, and further investigated to understand whether the associations found between viruses and Alzheimer's disease or dementia are mechanistically related," she said, noting the difficulty of assessing such associations in current models or in individuals for a number of reasons.

However, "the COVID-19 pandemic has created an opportunity to study the relationships between different viruses and Alzheimer's disease and other dementias by following individuals in a more routine and well-supervised manner," she added.

In fact, the Alzheimer's Association is working with a large global network of researchers to answer some of these questions related to COVID-19. "The lessons we learn and share can help us understand how other viruses are, or are not, linked to Alzheimer's disease and other dementias."

The study was funded by the National Institutes of Health.

The article was originally published on Medscape.com under the title: Mechanistic Link Between Herpes Virus, Alzheimer's Revealed?

Note from the editor. The virus hypothesis underlying Alzheimer’s disease has been around for more than twenty years but always received very low consideration from the neurobiologist community. This very first new step is providing novel evidence that the beta-amyloid is not the only pathway to investigate.

Paris, August 24, 2022.

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