More Evidence That Gum Disease May Play a Role in Alzheimer's Disease

By Megan Brooks

April 15, 2021

NEW YORK (Reuters Health) - Older cognitively healthy adults with more harmful than healthy bacteria in their gums are more likely to have biomarkers of amyloidosis in their cerebrospinal fluid (CSF), a new study has found.

"Amyloid-beta in brain is essential for the diagnosis of Alzheimer's disease and it is thought to be the first protein to accumulate in advance of clinical symptoms. Brain amyloid-beta can be estimated from CSF as increased brain levels are found with decreased CSF levels," lead author Dr. Angela Kamer of NYU College of Dentistry told Reuters Health by email.

"Our study showed for the first time an association between subgingival (under the gum line) bacteria and reduced CSF amyloid-beta in cognitively normal elderly people. The uniqueness of our findings is showing the importance of the balance between healthy and harmful bacteria in the homeostasis of amyloid-beta," Dr. Kamer said.

She and her colleagues studied 48 adults aged 65 and older with normal cognitive function. They collected subgingival bacterial samples and quantified bacteria known to be harmful and healthy to oral health. They also evaluated AD biomarkers of amyloid-beta and tau in CSF obtained via lumbar puncture.

At genera and species levels, higher imbalance in subgingival bacteria, with a ratio favoring harmful to healthy bacteria, was associated with reduced CSF amyloid-beta-42 (P=0.002 and P=0.01, respectively) but not with CSF phosphorylated tau, the researchers report in Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring.

This finding supports the hypothesis of periodontal dysbiotic effects on AD pathology is an early event, the researchers say.

"High levels of healthy bacteria maintain bacterial balance; they decrease subgingival and therefore systemic inflammation; and contribute to the nitrite oxide production known for its health effects," they explain in their paper.

High levels of healthy bacteria can also inhibit the production of virulent factors by other bacteria and reestablish bacterial balance. "In this environment, fewer pathogenic bacteria would escape the subgingival environment and travel to the brain. Healthy bacteria may also access the circulation and brain and exert anti-inflammatory effects there," they add.

"Maintaining periodontal/oral health is of paramount importance for the whole body as it is known to protect against heart disease and diabetes. Now it appears that there could be protection from Alzheimer's. Good oral hygiene, frequent visits to the dentist, prevention and treatment of your periodontal disease are just a few steps," Dr. Kamer told Reuters Health.

"This was a cross-sectional study and therefore it cannot conclude whether oral bacteria can cause amyloidosis. Longitudinal studies and in particular periodontal intervention studies could better reveal the relationship between oral bacteria and brain amyloidosis," she cautioned.

Dr. Ryan Demmer of the Division of Epidemiology and Community Health at the University of Minnesota, in Minneapolis, who wasn't involved in the research, told Reuters Health by email, "This is a valuable biomarker study that links direct measures of the oral microbiome to important biomarkers of future Alzheimer's disease."

Last year, Dr. Demmer and his colleagues reported results of a study showing that periodontal disease was modestly associated with incident mild cognitive impairment and dementia in a community-based cohort of black and white participants in the Atherosclerosis Risk in Communities (ARIC) study (

As for the current study, Dr. Demmer said, "The fact that data were collected in people without cognitive impairment is a strength and future, larger studies that can link oral microbiota to the development of incident Alzheimer's and other dementias will be important to confirm the validity of these findings."

This study was supported by grants from the National Institutes of Health and the Alzheimer's Association.

SOURCE: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, online April 12, 2021.