How Alzheimer’s functions and why it develops is still a source of huge mystery, but by following its biochemical footsteps researchers are being led to some strangely promising places. In newly published research, scientists have uncovered evidence of how bacterial toxins stemming from poor oral hygiene can make their way into the brain and may well contribute to the disease, and others like it.

Earlier research has uncovered the somewhat surprising role that gum disease may play in the development of Alzheimer’s disease. A significant study published back in January shone a light on a little bacterium called Porphyromonas gingivalis (Pg), responsible for a common form of gum disease, demonstrating how infection in mouse models can see it take hold in the brain and cause the kind of neuronal damage seen in Alzheimer’s patients.

Now researchers from the University of Louisville School of Dentistry and Poland’s University in Krakow have followed this line of investigation further. In what they describe as the strongest evidence of this link yet, the scientists explored the relationship between Pg and Alzheimer’s by examining brain samples of deceased subjects, both with and without the disease.

All subjects were around the same age when they died, but the team found Pg to be much more common in the samples taken from those with Alzheimer’s, with its DNA fingerprint and key toxins called gingipains revealing its presence. Interestingly, these toxins are also linked with other conditions, such as rheumatoid arthritis and aspiration pneumonia, suggesting staving them off could have a multitude of health benefits.

“Oral hygiene is very important throughout our life, not only for having a beautiful smile but also to decrease the risk of many serious diseases,” says Jan Potempa, PhD, DSc, a professor at the University of Louisville School of Dentistry and head of the department of microbiology at Jagiellonian University in Krakow, Poland. “People with genetic risk factors that make them susceptible to rheumatoid arthritis or Alzheimer’s disease should be extremely concerned with preventing gum disease.”

In terms of developing drugs to intervene in the pathway of Pg to the brain, the wheels are already very much in motion. Private company Cortexyme, which was behind the research published in Science Advances earlier in the year, demonstrated that its compound COR388 could block gingipain activity in mice and cut down on symptoms of Alzheimer’s, including reducing neuroinflammation and blocking amyloid protein production.

This experimental drug is currently in phase 1 clinical trials, with phase 2 and 3 human trials planned for later in the year. Cortexyme says the early signs are promising but it will take years before solid evidence can be gathered on the true validity of this young and promising hypothesis.

“P. gingivalis‘s main toxins, the enzymes the bacterium need to exert its devilish tasks, are good targets for potential new medical interventions to counteract a variety of diseases,” says Potempa. “The beauty of such approaches in comparison to antibiotics is that such interventions are aimed only at key pathogens, leaving alone good, commensal bacteria, which we need.”

The researchers presented their work at the 2019 Experimental Biology meeting between April 6 and 9 in Orlando, while an abstract of the paper is available online here.

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