Is gum disease linked to Alzheimer's disease?

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Newsweek

A bacteria that causes gum disease has been linked to Alzheimer’s disease in a study scientists believe could pave the way for new treatments targeting the debilitating condition.  

An enzyme called gingipains, which the Porphyromonas gingivalis (P. gingivalis) bacteria gives off, is the “main cause of Alzheimer’s disease,” Dr. Steve Dominy, study author and associate professor at University of California, told Newsweek. However, other experts in the field responded cautiously to the findings published in the journal Science Advances.

Read more: Common herpes virus could cause 50 percent of Alzheimer's disease cases, expert says

Researchers first compared the brain tissue of patients with and without Alzheimer’s disease. They found 96 percent of 53 patients with the condition had RgpB, or a form of the gingipains enzyme known as arginine-gingipain. And 91 percent of 54 patients tested positive for Kgp, or lysine-gingipain. These were detected at levels significantly higher than the control samples, the authors said. 

DNA tests on three brains with Alzheimer’s disease and six healthy brains also had the gene associated with P. gingivalis in their tissue. The team also examined the cerebrospinal fluid and saliva of 10 patients believed to have Alzheimer’s disease, and found the P. gingivalis gene hmuY in seven, and P. gingivalis itself in all of them.

And in an experiment on mice, those dosed with gingipains had higher levels of the hallmark Alzheimer’s protein, amyloid beta, and greater damage to their neurons than those who didn’t. What’s more, when mice were treated with a drug blocking the enzymes, the neurodegeneration stopped.

Around half of adults have periodontitis. Some 10 percent experience a severe version of the disease, which erodes the gums and the bones that keep our teeth in place, the authors said. If the findings are shown to be correct, this could offer one reason for why 5.7 million Americans are currently living with Alzheimer’s disease: a figure set to rise to 14 million by 2050.

The researchers hope a drug that inhibits the spread of P. gingivalis in the brain could slow the symptoms of the neurodegenerative disorder.

Referring to tau, a protein associated with Alzheimer's disease, Dominy told Newsweek: “Studies reported in our paper indicate that P. gingivalis and gingipains can directly kill neurons, damage tau, elevate levels of beta amyloid, and increase markers of neuroinflammation.”

“In addition, our finding of DNA from P. gingivalis in the cerebrospinal fluid of living AD patients provides further evidence that P. gingivalis infects the central nervous system. Based on these findings, we believe that P. gingivalis is the main cause of Alzheimer’s disease, and the gingipains are the main drivers of Alzheimer’s disease pathology.

“These findings provide a new strategy for Alzheimer’s treatment by specifically targeting P. gingivalis and gingipains instead of amyloid beta,” he said.

However, he said the study was limited because the team has not yet determined if different strains of P. gingivalis are more virulent than others in causing brain infection. “This remains an area of active investigation,” he said.

Those concerned that poor dental health could increase their risk of Alzheimer’s disease are advised to practice good oral hygiene to preclude the prevalence of P. gingivalis in the mouth, said Dominy. But he stressed this won't prevent the brain from becoming infected by P. gingivalis.

"That is why we have created highly potent, brain penetrant, anti-gingipain small molecules to target P. gingivalis and gingipians in the brain," he said. 

Dr. David Reynolds, a chief scientific officer at the charity Alzheimer’s Research UK who did not work on the paper, commented: “The presence of a single type of bacteria is extremely unlikely to be the only cause of the condition.”

Describing the study as “well-conducted,” he explained: “Previously the P. gingivalis bacteria associated with gum disease has been found in the brains of people with Alzheimer’s but it remains unclear what role, if any, it plays in the development of the disease.”  

“We know diseases like Alzheimer’s are complex and have several different causes, but strong genetic evidence indicates that factors other than bacterial infections are central to the development of Alzheimer’s, so these new findings need to be taken in the context of this existing research,” he argued.

However, he welcomed the avenue of inquiry as no new drugs targeting Alzheimer’s have been released for over 15 years.

“It’s important we carefully assess all new potential treatments, and this drug is currently in an early phase clinical trial to establish if it is safe for people. We will have to see the outcome of this ongoing trial before we know more about its potential as a treatment for Alzheimer’s," he said. 

Studies in the past have also associated the little-understood disease to the virus which cases herpes.