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Research roundup: A look at recent work by Upstate scientists

Is herpesvirus connected to Alzheimer’s disease?

In the ongoing search to understand why someone develops Alzheimer’s disease, scientists have explored many potential causes, including particular genes and a history of head injuries. 

There is also thought to be a connection to a herpesvirus. 

Nine different herpesviruses spread easily, primarily through saliva or other body fluids. Once infected, a person has that particular herpesvirus forever. 

“For the most part, if you have a healthy, competent immune system, the viruses are fairly benign. They don’t cause a lot of issues. It’s only after times of stress or immune suppression that the viruses come back and cause problems,” explained Eain Murphy, PhD, an associate professor of microbiology and immunology at Upstate. 

“On a regular basis, anybody walking around is harboring — I believe the current estimates are — 3.2 different herpesviruses,” he said. (Click here for a podcast interview with Murphy on his work.)

Murphy has focused on two types that replicate in nerve cells since 2018, when a flurry of research was published, including one study showing herpesvirus in the areas of the brain where Alzheimer’s was active, but not in the areas where Alzheimer’s was not active. 

Three conditions are present in Alzheimer’s. One is inflammation, which Murphy points out can be caused by viral infections. The second is beta-amyloid protein that accumulates outside of the nerve cells, which other researchers have shown increases with herpesvirus infections. 

The third condition is the accumulation of tau protein inside the nerve cells. 

“That’s where I started research projects saying, ‘Will infection of these neurons cause accumulation of tau inside the cells?’ And, in fact, that is the case,” Murphy said. 

“I don’t know if herpes simplex virus infection, alone, is sufficient for promoting the whole disease. I would strongly lay the claim that I think it’s definitely involved,” he said, “but there could easily also be environmental factors or genetic factors we haven’t identified yet.” 


Study finds daily cannabis use reduces pain tolerance

People who use cannabis daily for chronic pain are at risk of addiction, but they may also be lowering their tolerance for pain, according to research published in the American Journal of Addictions by Yanli Zhang-James, MD, PhD, and Brian Johnson, MD, from Upstate’s department of psychiatry and behavioral sciences. 

“Reduced tolerance to pain is not new for other drugs like opioids, alcohol and nicotine. But it’s the first time that we reported that this also happens to people who chronically use cannabis,” said Zhang-James, a research associate professor. “This is really important because it’s becoming increasingly widely accepted and considered a relatively safe drug to use for pain, but people should still be aware that it comes with certain risks.” (Click here to hear James and Johnson describe their work in a podcast interview.)

Assisted by medical student Dennis Grapsas and volunteer Evelyn Wyon, the researchers examined patient medical records from the past 10 years. They compared patients with chronic pain who used cannabis every day with patients who inhaled tobacco and patients who never used cannabis or tobacco. 

For an objective measure of pain tolerance, they used the cold pressor time test. “It’s a beer cooler full of ice water, and there’s an aquarium circulating pump,” explained Johnson, a clinical professor emeritus who previously served as director of addiction medicine. “The patient puts their forearm in, and it really hurts. We just time how long the patient is able to keep their arm under the ice.” 

Johnson and Zhang-James would like to learn in future research how quickly an increased sensitivity to pain develops, and also whether the sensitivity becomes permanent. “All we can tell you right now is anything that helps with pain short term is going to worsen it long term,” he said. 


Alternative treatment shows promise against risky infection

Clostridioides difficile, or C. diff, is a potentially life-threatening diarrheal illness. Doctors typically prescribe antibiotics, which are effective but which also increase the person’s risk of a repeated C. diff infection. 

“If a person has a C. diff infection for the first time in their life, there’s about a 25% chance that they will have another one. But if they get treated for that other one with antibiotics, the chances of having another one is about 40%. And if you have C. diff two times, the chances of getting a third is about 60%, which is really high,” says Aamer Imdad, MBBS, an Upstate graduate who was a faculty member specializing in nutrition and pediatric gastroenterology. Today he’s an assistant professor of pediatrics at University of Iowa and remains a visiting faculty member at Upstate.

“The antibiotics not only help treat, but behind the scenes it may actually exacerbate the problem in the long term,” he said.

The name of the problem is dysbiosis, an imbalance between the good bacteria and the bad bacteria that exist in a person’s gut. Imdad has found a possible solution: stool transplants. 

“Fecal microbiota (micro-organisms) transplantation reverses that dysbiosis because we essentially take stool from a healthy person who does not have dysbiosis, and we transplant that to a patient who seems to have dysbiosis and is getting these recurrent C. diff infections because of that,” he explains. (Hear Imdad explain his work in a podcast interview; click here.)

In a study that will inform guidelines from the American Gastroenterology Association, Imdad’s team found that stool transplants helped resolve current C. diff infections more often than antibiotics. 

About 75% of patients got better after a single transplant. If they had another recurrence and had a second transplant, the efficacy grew to up to 92%. As Imdad points out, “there are very few interventions in medicine that are as effective as fecal microbiota transplantation for treatment of recurrent C. diff.” 

This article appears in the 2024 Upstate Health magazine, Issue 1.