Could Herpes Virus Play a Role in Alzheimer's

Could Herpes Virus Play a Role in Alzheimer's

Viruses could play a key role in the development of Alzheimer's disease, a new study suggests.

Brains riddled with Alzheimer's disease contain high levels of two strains of human herpes virus, researchers discovered.

Human herpes virus 6 and 7 were found in Alzheimer's-affected brains at levels up to twice as high as in those without Alzheimer's, the scientists reported Thursday.

A detailed genetic analysis found that herpes viruses appear to interact with human genes previously linked to Alzheimer's, said senior author Joel Dudley.

"It appeared the virus was acting in the networks or biological pathways with many known Alzheimer's genes," said Dudley, director of the Institute for Next Generation Healthcare at the Icahn School of Medicine at Mount Sinai, in New York City.

"It suggests that the viral activity was activating or suppressing genes that are in close contact with known Alzheimer's genes," he added.

These results could provide a new avenue of research aimed at preventing and treating Alzheimer's, said Keith Fargo, director of scientific programs and outreach for the Alzheimer's Association.

"Alzheimer's disease is not contagious," Fargo said. "However, if viruses or other infections are confirmed to have roles in Alzheimer's, it may enable researchers to find new anti-viral or immune therapies to treat or prevent the disease."

Herpes viruses 6 and 7 are widely present in humans, but poorly understood. They infect nearly every human, typically during infancy, and have been closely linked to the childhood rash called roseola, according to the HHV-6 Foundation.

Like other herpes viruses -- herpes simplex, chickenpox and Epstein Barr virus -- strains 6A and 7 linger dormant in the body and can reactivate later in life. The strains have been linked to encephalitis and other chronic conditions.

"It's known to be particularly virulent in neurons and has been associated with other neurological conditions," Dudley said. "Everybody's exposed to it, but it's pretty enigmatic in terms of how it might be contributing to health."

Dudley and his colleagues stumbled across this possible viral link to Alzheimer's during an analysis intended to find ways that drugs used to treat other illnesses could be repurposed for treating the dreaded neurodegenerative disease.

The research team had been mapping and comparing the biological networks that underlie Alzheimer's disease, based on detailed genetic analyses of more than 600 brain tissue samples.

The investigators found that the Alzheimer's disease process is likely affected by a complex series of interactions between viral and human genetics.

"We were able to build a social network of the virus and the host genes, to see who is friends with who," Dudley said.

These models helped explain how the viral genes are operating in context of the host's genes. "When we built those network models, we found that the virus/host interaction contained many known Alzheimer's genes," he said.

To test what they found, the researchers performed further genetic analysis on another 800 brain samples collected by the Mayo Clinic and Rush Alzheimer's Disease Center. In these samples, the scientists saw a persistent increase in human herpes viruses 6A and 7 in the brains of Alzheimer's patients.

"This opens up the door for looking for new therapies that target the immune system in Alzheimer's," Dudley said.

Before that can happen, though, "we need to come up with better tools to identify those with Alzheimer's who have high-risk genetics who also have virus exposure in brain," Dudley added.

"We want to be able to identify folks who would benefit most from a trial involving antiretroviral medications, and we don't have those tools yet," he added.

Fargo said the new study "increases the credibility" of previous theories that have linked infectious disease and Alzheimer's.

"Possible roles for microbes and viruses in Alzheimer's disease have been suggested and studied for decades, but previous research has not explained how they may be connected," Fargo said. "This is the first study to provide evidence based on multiple, large data sets that lends support to this idea."

But Fargo noted that much follow-up work is needed to better understand the association uncovered by this new research.

"As an illustration, we simply don't know at this point if Alzheimer's disease-related brain changes create added susceptibility to these viruses, or if infection by these viruses creates additional risk of Alzheimer's disease. Or are there additional factors involved? This is the challenge for researchers," Fargo said.

The findings were published online June 21 in the journal Neuron.

More information

The HHV-6 Foundation has more about human herpes virus 6.

SOURCES: Joel Dudley, Ph.D., director, Institute for Next Generation Healthcare, Icahn School of Medicine at Mount Sinai, New York City; Keith Fargo, Ph.D., director, Scientific Programs and Outreach, Alzheimer's Association; June 21, 2018, Neuron, online

 
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