Gum disease linked to buildup of Alzheimer’s plaque formation

Oral bacteria traveling to the brain causes brain cells to become dysfunctional, promoting neuroinflammation

Peer-Reviewed Publication

FORSYTH INSTITUTE

Cambridge, Mass. - Although most people don’t associate oral disease with serious health problems, increasing evidence shows that oral bacteria play a significant role in systemic diseases like colon cancer and heart disease. Now, new research from the Forsyth Institute shows a link between periodontal (gum) disease and the formation of amyloid plaque, a hallmark of Alzheimer’s disease.

In their paper, “Microglial cell response to experimental periodontal disease,” published in the Journal of Neuroinflammation, Forsyth scientists and their collaborators at Boston University demonstrate that gum disease can lead to changes in brain cells called microglial cells, which are responsible for defending the brain from amyloid plaque. This plaque is a type of protein that is associated with cell death, and cognitive decline in people with Alzheimer’s. The study provides important insight into how oral bacteria makes its way to the brain, and the role of neuroinflammation in Alzheimer’s disease.

“We knew from one of our previous studies that inflammation associated with gum disease activates an inflammatory response in the brain,” said Dr. Alpdogan Kantarci, senior member of staff at Forsyth and a senior author of the study. “In this study, we were asking the question, can oral bacteria cause a change in the brain cells?”

The microglial cells the researchers studied are a type of white blood cell responsible for digesting amyloid plaque. Forsyth scientists found that when exposed to oral bacteria the microglial cells became overstimulated and ate too much. “They basically became obese” Dr. Kantarci said. “They no longer could digest plaque formations.”

The finding is significant for showing the impact of gum disease on systemic health. Gum disease causes lesions to develop between the gums and teeth. The area of this lesion is the size of your palm. Dr. Kantarci explained, “It’s an open wound that allows the bacteria in your mouth to enter your bloodstream and circulate to other parts of your body.” These bacteria can pass through the blood/brain barrier and stimulate the microglial cells in your brain.

Using mouse oral bacteria to cause gum disease in lab mice, the scientists were able to track periodontal disease progression in mice and confirm that the bacteria had traveled to the brain.  

They then isolated the brain microglial cells and exposed them to the oral bacteria. This exposure stimulated the microglial cells, activated neuroinflammation and changed how microglial cells dealt with amyloid plaques.

“Recognizing how oral bacteria causes neuroinflammation will help us to develop much more targeted strategies,” said Dr. Kantarci. “This study suggests that in order to prevent neuroinflammation and neurodegeneration, it will be critical to control the oral inflammation associated with periodontal disease. The mouth is part of the body and if you don’t take care of oral inflammation and infection, you cannot really prevent systemic diseases, like Alzheimer’s, in a reproducible way.”

This study is the first time that scientists caused periodontal disease with mouse-specific bacteria and could study the effects of same-species oral microbiome on the brain. Having same-species bacteria and cells brings the test closer to replicating what the process looks like in humans.

Taking good care of your teeth may be good for your brain

 

 Taking good care of your teeth may be linked to better brain health, according to a study published in the July 5, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study found that gum disease and tooth loss were linked to brain shrinkage in the hippocampus, which plays a role in memory and Alzheimer’s disease. The study does not prove that gum disease or tooth loss causes Alzheimer’s disease; it only shows an association.

“Tooth loss and gum disease, which is inflammation of the tissue around the teeth that can cause shrinkage of the gums and loosening of the teeth, are very common, so evaluating a potential link with dementia is incredibly important,” said study author Satoshi Yamaguchi, PhD, DDS, of Tohoku University in Sendai, Japan. “Our study found that these conditions may play a role in the health of the brain area that controls thinking and memory, giving people another reason to take better care of their teeth.”

The study involved 172 people with an average age of 67 who did not have memory problems at the beginning of the study.

Participants had dental exams and took memory tests at the beginning of the study. They also had brain scans to measure volume of the hippocampus at the beginning of the study and again four years later.

For each participant, researchers counted the number of teeth and checked for gum disease by looking at periodontal probing depth, a measurement of the gum tissue. Healthy readings are from one to three millimeters.

Mild gum disease involves probing depths of three or four millimeters in several areas, while severe gum disease involves probing depths of five or six millimeters in several areas as well as more bone loss and can cause teeth to become loose and eventually fall out.

Researchers found that the number of teeth and amount of gum disease was linked to changes in the left hippocampus of the brain.

For people with mild gum disease having fewer teeth was associated with a faster rate of brain shrinkage in the left hippocampus.

However, for people with severe gum disease having more teeth was associated with a faster rate of brain shrinkage in the same area of the brain.

After adjusting for age, researchers found that for people with mild gum disease, the increase in the rate of brain shrinkage due to one less tooth was equivalent to nearly one year of brain aging. Conversely, for people with severe gum disease the increase in brain shrinkage due to one more tooth was equivalent to 1.3 years of brain aging.

“These results highlight the importance of preserving the health of the teeth and not just retaining the teeth,” Yamaguchi said. “The findings suggest that retaining teeth with severe gum disease is associated with brain atrophy. Controlling the progression of gum disease through regular dental visits is crucial, and teeth with severe gum disease may need to be extracted and replaced with appropriate prosthetic devices.”

Yamaguchi said future studies are needed with larger groups of people. Another limitation of the study is that it was conducted in one region of Japan, so the results may not be generalizable to other locations.

The study was supported by the Japanese Ministry of Education, Culture, Sports, Science and Technology; Keio University; Japan Arteriosclerosis Prevention Fund; Japanese Ministry of Health, Labor, and Welfare; Teikyo University; Pfizer Japan; Bayer Yakuhin; Chugai Pharmaceutical; Daiichi Sankyo; Astellas Pharma; Takeda Pharmaceutical; Health Care Science Institute; Health Science Center; and Takeda Science Foundation.

Learn more about Alzheimer’s disease at BrainandLife.org, home of the American Academy of Neurology’s free patient and caregiver magazine focused on the intersection of neurologic disease and brain health. Follow Brain & Life® on Facebook, Twitter and Instagram.

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The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with over 40,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.

For more information about the American Academy of Neurology, visit AAN.com or find us on Facebook, Twitter, Instagram, LinkedIn and YouTube.