According to new research published in the journal Science Advances, there is a significant link between the bacterium Porphyromonas gingivalis – the main cause of chronic gum disease – and Alzheimer’s.
A team of scientists from the University of Louisville found P. gingivalis in the brains of deceased people who suffered from Alzheimer’s. They also discovered the bacterium’s DNA in their spinal fluid and toxic enzymes called gingipains, which are produced by the microbe, in their brains. The same brains also contained higher levels of tau protein and ubiquitin, which are both linked to Alzheimer’s disease.
Interestingly, the brains of 50 control bodies, who were elderly but did not suffer from Alzheimer’s, contained low levels of gingipains. This is important because previous studies have found a link between P. gingivalis and Alzheimer’s before, but it’s been unclear whether poor oral care is just a side effect of dementia. These findings suggest that it’s the other way around, and that the control patients might have gone on to develop the disease if they had lived longer and the gingipains had built up more.
The team then turned to mice to see whether P. gingivalis enters the brain following a mouth infection. Over six weeks, they established infections in the mouths of otherwise healthy mice and indeed discovered the presence of the bacterium in their brains. They also found dying nerve cells and high levels of beta-amyloid protein, a hallmark of Alzheimer’s disease.
While the new results are certainly exciting, and the study is the largest ever to investigate the link between Alzheimer’s and P. gingivalis, it’s important to note that it doesn’t prove the bacterium causes Alzheimer’s, just that it is likely a contributing factor.
“We now have strong evidence connecting P. gingivalis and Alzheimer’s pathogenesis, but more research needs to be done before P. gingivalis is explicitly implicated in the causation or morbidity of Alzheimer’s disease,” said study co-author Jan Potempa.
“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,” added David Reynolds, Chief Scientific Officer at Alzheimer’s Research UK.
The team even managed to find a way to kill P. gingivalis in the brains of mice. They used a compound that targeted the gingipains, which likely supply nutrients to the bacteria, to successfully kill off the bacteria, reducing neurodegeneration and the formation of beta-amyloid protein.
Biotech start-up Cortexyme, Inc., who sponsored the new research, has previously shown a similar drug to be safe and tolerable in both healthy old people and those with Alzheimer’s in a Phase 1 clinical trial. They hope to conduct a Phase 2 trial to further test out their drug soon.