DCG researcher studying gum disease, Alzheimer’s awarded $2.8M grant

Ranya El Sayed, PhD, assistant professor of Periodontics in Augusta University’s Dental College of Georgia, has been awarded a $2.8 million grant from the National Institute on Aging to lead a study examining the connection between periodontitis, or gum disease, and Alzheimer’s disease.

The study, “The role of oral microbially-induced exosomes in Alzheimer’s disease pathogenesis,” aims to explore the link between periodontal infections and increased risk of dementia, focusing on the potential mechanisms by which oral pathogens may invade the central nervous system.

“Research shows a significant relationship between gum disease and Alzheimer’s disease, but the biological reasons and mechanisms underlying this link are not yet understood,” El Sayed said. “A protein from P. gingivalis, a known periodontal pathogen, was detected in the brains of deceased Alzheimer’s patients. But we don’t know how it happens. Is it simply an association, or is there a direct cause and effect?”

The team believes p. gingivalis might make people with gum disease, who are already at risk genetically, more susceptible to developing Alzheimer’s.

Alzheimer’s disease is currently the sixth leading cause of death in the U.S., but the exact process by which the disease develops and progresses remains unknown.

“The NIH R01 award is a significant achievement for Dr. El Sayed and a proud milestone for the Dental College of Georgia,” said Babak Baban, PhD, DCG’s associate dean for Research. “This recognition underscores the vital role of funding in advancing innovative, transdisciplinary research that bridges oral health and systemic diseases. The Center for Excellence in Research, Scholarship, and Innovation at our college is dedicated to nurturing such impactful research, fostering collaboration and driving progress in both dental and biomedical sciences to tackle pressing health challenges.”

El Sayed and her team believe that infections of the gums caused by p. gingivalis result in the release of small vesicles called [RE1] exosomes within the mouths of patients with gum disease. These vesicles travel through the gums, causing inflammation and bone loss, eventually entering the bloodstream. Due to their small size, they can cross the blood-brain barrier – the brain’s protective membrane – and enter the brain tissue. There, they are taken up by the brain’s immune cells, causing inflammation, and ultimately leading to neuron degeneration.

To test this, researchers will use mouse models and will induce periodontitis in one group of mice and then transfer extracted vesicles from infected tissue to another group. Finally, they will monitor the behavior of the mice for signs of dementia.

The team hopes answering the “how” of this process will enable patients to put precautions in place. Periodontal disease affects nearly half of the U.S. population, with 10% having a severe form. But Alzheimer’s disease is complex, arising from a mix of causes like genetics, inflammation and harmful protein buildup in the brain. 

“This is the work of years by Dr. El Sayed and her team; and a great achievement for Augusta University in general and the DCG,” said Mahmoud Elashiry, PhD, assistant professor of Periodontics and a co-investigator on the grant. “When we understand how these processes intersect, it will be easier to find a cure.”

Joining El Sayed and Elashiry as co-investigators on the grant are Qin Wang, MD, PhD, professor in the Department of Neuroscience and Regenerative Medicine and director of program for Alzheimer’s Therapeutic Discovery at AU’s Medical College of Georgia; Alexis Stranahan, PhD, associate professor in MCG’s Department of Neuroscience and Regenerative Medicine; and Jie Chen, PhD, associate dean of Academic and Student Affairs in Augusta University’s School of Public Health.

Consultants on this project include Allan Levey, MD, PhD, professor of Psychiatry and Behavioral Sciences at Emory University; Yutao Liu, MD, PhD, and Mark Hamrick, PhD, professors in the MCG Department of Cellular Biology and Anatomy; Alvin Terry, PhD, professor and chair of MCG Department of Pharmacology and Toxicology; and Christopher Cutler, DDS, professor emeritus in DCG’s Periodontics Department.