Alzheimer’s: Griffin Pioneers Role of Neuroinflammation

David Robinson

Back  in  the mid-1980s Sue Griffin, Ph.D., was having a hard time attracting interest in her radical theory about Alzheimer’s disease.

Then she visited UAMS, where she presented her ideas about the role of inflammation in causing the brain’s neurons to self-destruct. Among those listening was the late Robert Fiser, M.D., then-chair of the Department of Pediatrics in the College of Medicine. 

“He said, ‘If you can’t get support from anywhere else, I will support you,’” said Griffin, who was at the University of Texas Southwestern in Dallas. “I was enchanted by that.” 

Also, collaborators at UAMS generously offered her the resources to study Down syndrome pathology, which helped prove a key part of her Alzheimer’s theory.   

Griffin, who sealed her legacy with her breakthrough discovery about Alzheimer’s disease, is a pioneer in the field of neuroinflammation. After joining UAMS in 1986, she published a landmark study in 1989 describing how inflammation in the brain’s neurons can provoke an out-of-control immune response. During such a response, neurons continue to release a molecule identified by Griffin (Interleukin-1) that ultimately leads to the creation of plaque that kills off more and more brain cells.

“The response has a purpose which is good, but sometimes it’s like turning a knob too far in the right direction – you break the connection,” she said.  

“It’s like turning a knob too far in the right direction – you break the connection.”
Ten years later, the mechanisms that keep the cycle going were discovered by UAMS’ Steve Barger, Ph.D., her collaborator since 1995.     

After joining UAMS, Griffin had more hurdles to overcome. Although she was an established National Institutes of Health (NIH)-funded brain/Alzheimer’s researcher, her Alzheimer’s discovery was rejected by some established Alzheimer’s researchers who had their own theories about the disease and its causes.

She also had to overcome doubt that UAMS was capable of leading her proposed Alzheimer’s research program. To earn the first two years of NIH funding, she had to submit her application through a collaborator at New York University. 

Griffin and her chief collaborator at the time, Robert E. Mrak, M.D., Ph.D., proved they were up to the task. The Alzheimer’s program at UAMS has earned NIH grant awards continuously since 1991. In 2004, Griffin and Mrak again had to convince critics of their legitimacy when they were among the first to start an open-source scientific publication: the Journal of Neuroinflammation. Today the journal is an international success. 

Many scientists have since confirmed her findings, and today most in the field accept her theory. In fact, several studies have found that regular use of anti-inflammatory drugs like ibuprofen (Advil) and naproxen for other conditions sharply reduces chances of developing Alzheimer’s. 

Today Griffin is working with a number of collaborators to find ways to prevent Alzheimer’s. They include UAMS’ Peter Crooks, Ph.D., a world-renowned drug developer, who is studying drugs that may inhibit inflammation. 

About 10-12 percent of people are genetically predisposed to experience the out-of-control Alzheimer’s-inducing cycle as their neurons detect inflammation – usually later in life. Still, Griffin believes it’s possible through lifestyle choices to prevent or delay the inflammatory responses that develops into Alzheimer’s. 

“Don’t get fat,” she said. “Belly fat, type II diabetes, no exercise – all are associated with inflammation. Even if you are genetically predisposed to Alzheimer’s, you can delay it with a healthy, active lifestyle, and keeping your brain active and challenged.”