MAY 11, 2020 6:42 AM PDT

3D Cell Culture Model Suggests Herpes Can Cause Alzheimer's

WRITTEN BY: Carmen Leitch

Alzheimer's disease (AD) is a common form of dementia that is thought to affect as many as 5.5 million Americans and the incidence is increasing as the population ages. In some cases, the illness runs in families, which is called familial AD. When it's not linked to family history, it's called sporadic AD. For several years, research has suggested that various pathogens, including the herpes virus and bacterial infections, may be involved in the development of AD.

The disease can be especially difficult to study because it affects the brain. But researchers have created three-dimensional tissue culture models that can be used to model human organs on a simple, small scale in the lab. The process used in this study applies neurons to a collagen scaffold to foster the growth of neural tissue. The method enabled the scientists to investigate the relationship between herpes simplex virus I (HSV-1) infection and sporadic Alzheimer’s disease.

“Our brain tissue model allowed us to take a closer look at the potential causal relationship between herpes and Alzheimer’s disease, and the results were intriguing,” said David Kaplan, Stern Family Professor of Engineering and chair of the Department of Biomedical Engineering at Tufts’ School of Engineering.

Reporting in Science Advances, the researchers found that an HSV-1 infection was enough to trigger known features of Alzheimer's to develop.

“After just three days of herpes infection, we saw large and dense plaque formations of beta-amyloid protein, as well as increased expression of some of the enzymes responsible for generating the plaques. We observed neuron loss, neuroinflammation, and depressed signaling between neurons – everything we observe in patients. Never before have so many facets of the disease been replicated in vitro,” said Kaplan.

When the brain cells were treated with valacyclovir, an antiviral drug used to treat herpes infections, plaque formation and other disease markers were reduced.

The researchers assessed gene expression in brain tissue that was infected with HSV-1; over 40 genes that are associated with Alzheimer's disease were overexpressed in infected cells compared to uninfected cells. That included genes that code for enzymes that are known to play a role in amyloid plaque formation. Some of these genes may be useful for creating new AD treatments. Valacyclovir restored some of these expression levels to what was observed pre-infection.

“This is a model of Alzheimer’s disease which is very different from what other studies have used,” said the first author of the study Dana Cairns, a postdoctoral research associate in the Kaplan lab. “Most other studies relied on using genetic mutations in the neurons to induce Alzheimer’s disease-like phenotypes and ours does not, which is what really sets it apart. Our model using normal neurons allows us to show that herpes virus alone is sufficient to induce Alzheimer’s disease phenotypes.”

More research will be needed to understand the impact of the genetic changes that are induced in neurons by a herpes virus infection, and how we can use this data to create treatment options or prevent the disease. These findings are also supported by earlier research that used patient samples. 


Sources: Tufts University, Science Advances

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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