Researchers Investigate Connection Between Periodontitis and Alzheimer Disease

In 2020, the National Institute on Aging (NIA) Intramural Research Program team investigated possible links between periodontal diseases and dementia diagnoses and deaths via data collected by the United States Centers for Disease Control and Prevention from a large pool of subjects as part of a National Health and Nutrition Examination Survey. Participants received oral exams to pinpoint any signs of periodontal disease, as well as blood tests for antibodies against causative bacteria.^1,2

Of 19 bacteria analyzed for an association with a diagnosis of or death from Alzheimer disease (AD) or any other kind of dementia, the NIA researchers found Porphyromonas gingivalis to be the most common periodontal disease miscreant. In fact, it’s thought that beta-amyloid plaques, a hallmark of AD, may be produced in response to such an infection.^1,2

The researchers also associated antibodies mounted against P. gingivalis with AD diagnoses and deaths among those ages 65 and older. To make matters worse, P. gingivalis can cluster with other bacteria including Campylobacter rectus and Prevotella melaninogenica to further increase risks. But it was determined that more research is warranted.²

GRANT FUNDS MORE RESEARCH

The NIA recently awarded a $3.1 million grant to the New York University (NYU) College of Dentistry, to fund further research into the relationship between periodontitis and AD.^1,3

Xin Li, PhD, a professor of molecular pathobiology at NYU College of Dentistry is the principal investigator on the new study. She notes that while AD is a growing public health crisis, there is still much we don’t know. “We’re trying to understand if and how periodontitis promotes the pathogenesis of AD, which could offer clues on how to treat or prevent the disease,” says Li.³

INFLAMMATION IS KEY

Preliminary research has shown a dramatic increase in the metabolic byproduct, succinate, in the cerebrospinal fluid of mice with periodontitis. It has also revealed that microglial cells, immune cells of the central nervous system, express the succinate receptor (SUCNR1).³

Microglial cells are vital for brain and central nervous system homeostasis, playing important roles in response to infections and inflammation. The researchers found that when mice with periodontitis were genetically altered to inactivate SUCNR1, a reduction in pro-inflammatory cytokines and microglial activation followed.³

This has led to the hypothesis that elevated succinate in periodontitis leads directly to neurodegeneration through SUCNR1 activation in microglial cells, and indirectly through systemic inflammation and the creation of an imbalance in the oral microbiome. They plan to conduct a series of studies in cells and mice to examine how SUCNR1 activation in microglial cells modulates neuroinflammation.³

Says Li, “These studies are designed to identify the mechanism by which periodontitis increases succinate in cerebrospinal fluid and activates the succinate receptor in microglial cells to induce neuroinflammation and neurodegeneration. If we then find that targeting the succinate receptor reduces neuroinflammation and cognitive impairment in animal models, this may provide a potential new therapeutic target for AD.”³

REFERENCES

1. National Institute on Aging. Alzheimer’s disease fact sheet.
2. Beydoun M, Beydoun HA, Hossain S, El-Hajj ZW, Weiss J, Zonderman AB. Clinical and bacterial markers of periodontitis and their association with incident all-cause and Alzheimer’s disease dementia in a large national survey.
3. New York University. NYU Dentistry receives NIH grant to study Alzheimer’s and gum disease.