Molecular Medicine Israel

Gum Disease Could Drive Alzheimer’s: Study

An enzyme of the bacteria Porphyromonas gingivalis has been found in the brains of patients with the disorder, and causes neurodegeneration in mice.

Traces of the bacterium Porphyromonas gingivalis, which causes chronic gum disease, have been found in the brains of people who had Alzheimer’s disease. The result suggests the bacterium may play a role in driving the development of the disease, researchers reported yesterday (January 23) in Science Advances.

Researchers looked at brain tissue from autopsies of individuals with and without Alzheimer’s disease and found a majority of those with the disease had higher levels of an enzyme called gingipains, which is produced by P. gingivalis. They also studied the enzyme’s effects in the brains of mice, and found that it caused the animals to develop signs of Alzheimer’s. The results indicate gingipains is the “main cause of Alzheimer’s disease,” study coauthor Steve Dominy, a neurologist at Cortexyme, Inc., a company developing treatments for the disease, tells Newsweek. The new study is one of a growing number that suggest microbes play a role in Alzheimer’s disease.

See “Do Microbes Trigger Alzheimer’s Disease?”
“I’m fully on board with the idea that this microbe could be a contributing factor. I’m much less convinced that [it] causes Alzheimer’s disease,” Robert Moir, a neurobiologist at Massachusetts General Hospital in Boston who was not involved in the study, tells Science.

In the study, Dominy and his colleagues swabbed P. gingivalis onto the gums of healthy mice every other day for 6 weeks. The bacterium took hold, and the team later detected it in the mice’s brains, where they also found dying neurons and higher levels of β-amyloid protein than in control animals, indicating the infected animals had developed signs of Alzheimer’s disease. In cell cultures, different forms of the gingipain enzyme damaged tau, another protein associated with Alzheimer’s, and that damage may cause tau to develop into tangles, which are another indicator or Alzheimer’s neurodegeneration, the researchers found in additional experiments. The team also gave the mice a drug that bound to the gingipain enzyme. The drug cleared the infection from the animals’ brains and reduced β-amyloid production and neurodegeneration.

The study “is clearly very comprehensively approached,” James Noble, a neurologist at Columbia University who has studied the link between periodontal disease and Alzheimer’s but was not involved in the new work, tells Science. “These are strange ideas, but they seem to be getting some traction.”

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