NEW TARGET

A common oral infection may contribute to Alzheimer’s disease

The link could provide new insights for future treatments.
The link could provide new insights for future treatments.
Image: AP Photo/Haraz Ghanbari
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The idea that Alzheimer’s disease, the most common form of dementia, could be caused by an infectious disease is controversial, but it’s gaining credibility. Last year, for example, two major papers came out linking Alzheimer’s to common forms of the herpes virus, although it’s not yet clear how these viruses may work with a person’s genes to cause the disease.

Yesterday (Jan. 23), researchers published work suggesting that yet another common infection may exacerbate the progression of Alzheimer’s disease. Researchers led by a team at Cortexyme, a San Francisco-based startup pharmaceutical company, found evidence that the same bacteria that causes chronic gum infections may contribute to the buildup of the plaques and tau that are the hallmarks of Alzheimer’s disease. This work could open the door for new treatments that target this bacteria to save neurons.

Porphyromonas gingivalis is a bacteria that can cause periodontitis, or gum disease. Previous estimates suggest that about half of all US adults (paywall) have this bacterial infection, although only about 10% have severe cases that could lead to tooth decay. People who have periodontitis are also more likely to have Alzheimer’s disease, although it’s not clear if that’s because people living with dementia have a harder time maintaining oral hygiene or if there is some more causative explanation.

P. gingivalis doesn’t always remain confined to the mouth. It’s been found to reach the brain, where it may cause trouble. (Scientists suspect it gets transported there through white blood cells or the nerves leading up to the brain.)  One small study found evidence of the bacteria in the brains of people who died of Alzheimer’s disease. Late last year, scientists found that chronic P. gingivalis infections in mice led their brains to degenerate in ways similar to what happens in humans with Alzheimer’s.

This latest study is the first to show how P. gingivalis may work in the brain to exacerbate Alzheimer’s disease. The researchers looked at the brains of roughly 50 people who died of Alzheimer’s disease. Over 90% them had evidence of some of the proteins released by P. gingivalis, called gingipains. The researchers also looked at 50 brains from people who died without dementia, and found gingipains just over half the time. However, people who died of Alzheimer’s tended to have higher levels of the proteins. More gingipains correlated with more tau tangles, which are a characteristic of Alzheimer’s disease.

The team also infected mice with P. gingivalis to see if it could reach their brains. Sure enough, they were able to spot damage to their neurons similar to Alzheimer’s disease in humans.

Excitingly, they were able to reverse some of this early damage by giving the mice a dose of a protein that binds to some of the gingipains, effectively neutralizing them, and preventing them from damaging neurons.

This work doesn’t definitively show that P. gingivalis causes Alzheimer’s, but that it could accelerate damage from the disease in individuals who are already at higher risk of the disease, like those who have poor diets or certain genetic traits. (Although it’s always a good idea to avoid periodontitis with good brushing habits.) Developing drugs targeting gingipains could be future treatment for people who have developed early Alzheimer’s. In one small clinical trial, Cortexyme showed that one of these drugs could be tolerated by people with Alzheimer’s, although it will take significant work to show that it actually works against the disease.