Study shows how herpes viruses contribute to Alzheimer’s disease in aging brains

Researchers from the Genome Center of Cleveland Clinic outlined the path that Humane Herpes Simplex Virus-1 (HSV1) can use to contribute to Alzheimer’s disease in aging brains. Published in a report in Alzheimer & Dementia: The Journal of the Alzheimer’s AssociationResearchers also share two commercially available medicines approved by the FDA that reverse this route in a laboratory environment.

The findings are the first concrete evidence to support the rather controversial link between human herpes viruses (HHVs) and Alzheimer’s disease. Illustrating the potential for herpes to activate dementia aids, efforts to prevent and cure neurodegenerative disease, says senior author and director of the Genome Center Feixiong Cheng, PhD.

For most people, drawing up a herpes infection is only an uncomfortable or harmless fact of life. Many herpes viruses are individually present in a large percentage of people worldwide, which means that almost every person on earth is expected to contract at least three types of herpes viruses by maturity. Some of these viruses do not cause symptoms, while others only cause small diseases such as mono or chickenpox. Even after these diseases have disappeared, an infected person still wears herpes viruses for the rest of their lives with only small symptoms such as incidental cold sores.

Although herpes viruses are generally harmless when suppressed, the increasing evidence shows that our immune system can lose the ability to suppress them. This can of course happen as we get older, during pregnancy and after an illness. Recent research has shown that as herpes viruses become more active, they can activate diseases, including pregnancy complications, birth defects or developmental arrears in our children and even cancer.

It becomes clear that HSV and other herpes viruses are risk factors for diseases of old age that are displayed, Dr. Cheng. In detail, HSV-1 linked Alzheimer’s disease, but there was no explanation for how these phenomena were linked.

Dr. Cheng stated the hypothesis that latent HPV-1 infections can cause Alzheimer’s disease by immediately activating the transposable elements that the Cheng-Lab had previously connected to disease progression in aging brains. Transposable elements are small pieces of DNA that can activate to “jump” out of our chromosomes physically and randomly go to distant areas of our DNA. The elements again integrate into these new regions of our genome and disrupt the function of the genes they interrupt. Almost half of our DNA consists of transposable elements and the elements become more active as we get older.

After mapping all transposable elements associated with Alzheimer’s disease in aging brain, researchers analyzed four publicly available datasets that contain RNA sequence data of hundreds of healthy and alzheimer-like brain cells. The Cheng Lab received cooperation and helping interpret their data from Jae Jung, PhD, chairman of Infection Biology; James Leverenz, MD, formerly from the Lou Ruvo Center for Brain Health by Cleveland Clinic; and employees of Case Western Reserve University and the University of Nevada Las Vegas.

The team identified several TEs that were more strongly activated in brains affected by Alzheimer’s that contain HSV-RNA compared to uninfected or healthy brains. They then tested HSV-1 infected brain cells to see if the identified TETs were activated, as well as the effects on neuro inflammation and accumulation of proteins associated with Alzheimer’s disease.

The result was a step-by-step manual about the connection between HSV-1 and the characteristics of Alzheimer’s disease:

1. An individual contracts HSV-1, or their latent HSV-1 infection becomes more active as a natural consequence of age;
2. The HSV-1 are linked to transposable element (such as Line-1) activation;
3. The transposable elements disrupt important genetic processes in the brain that are associated with an accumulation of tau and similar Alzheimer-associated proteins, and;
4. The accumulated proteins contribute to inflammation and neurodegeneration.

The researchers then used artificial intelligence to analyze 80 million publicly available patient health files to see whether persons prescribed antiviral herpes medicines were prescribed later received fewer diagnoses from Alzheimer’s in life. The Herpes Medicines Valacyclovir and Aceclovir were associated with significantly reduced cases of Alzheimer’s disease. Treating laboratory models with these drugs seemed to turn the infection into Alzheimer’s disease, and mechanisticly supported them what they have observed in real patient data.

These results also suggest potential relationships between HSV-1 infection and Alzheimer’s disease and offer two potential candidates for medicines that can be treated for a disease that currently has no healing. We hope that, if widely applied, our findings can also offer new strategies for treating other neurological diseases related to herpes viruses or other viruses. “

Dr. Feixiong Cheng, senior author

This research was supported by subsidies from the National Institute on Aging (NIA).