In recent years, a growing number of scientific studies have supported an alarming hypothesis: Alzheimer’s disease isn’t just a disease, it’s an infection.
While the exact mechanisms of this infection are something researchers are still trying to isolate, numerous studies suggest that the deadly spread of Alzheimer’s disease goes far beyond what we used to think.
One such study, published in 2019, suggested what may be one of the most definitive clues yet to a bacterium to blame for Alzheimer’s, and it comes from a somewhat unexpected area: gum disease.
In a paper led by lead author Jan Potempa, a microbiologist at the University of Louisville, the researchers reported the discovery of Porphyromonas gingivalis – the pathogen behind chronic periodontitis (also known as gum disease) – in the brains of deceased Alzheimer’s patients.
It was not the first time that the two factors were linked, but the researchers went further.
In separate experiments with mice, oral infection with the pathogen led to colonization of the brain by the bacteria, along with increased production of amyloid beta (Aβ), the sticky proteins commonly associated with Alzheimer’s.
The research team, coordinated by pharmaceutical startup Cortexyme, which was co-founded by first author Stephen Dominy, did not claim to have discovered definitive evidence of Alzheimer’s causation.
But it was clear that they thought we had a strong line of inquiry here.
“Infectious agents have been implicated in the development and progression of Alzheimer’s disease before, but the evidence for causality has not been convincing,” Dominy said at the time.
“Now, for the first time, we have strong evidence connecting the intracellular Gram-negative pathogen, P. gingivalisand the pathogenesis of Alzheimer’s”.
In addition, the team identified toxic enzymes called gingipains secreted by the bacterium in the brains of Alzheimer’s patients, which correlated with two separate markers of the disease: the tau protein and a protein tag called ubiquitin.
But even more compelling, the team identified these toxic gum sores in the brains of deceased people who were never diagnosed with Alzheimer’s disease.
That’s important, because while P. gingivalis and disease have been linked before, it has never been known, simply put, whether gum disease causes Alzheimer’s disease or dementia leads to poor oral care.
The fact that low levels of gingipains were evident even in people who were never diagnosed with Alzheimer’s could be irrefutable evidence, suggesting that they might have developed the condition had they lived longer.
“Our identification of gingipain antigens in the brains of people with AD and also with AD pathology, but without a diagnosis of dementia, argues that brain infection with P. gingivalis It is not the result of poor dental care after the onset of dementia or a consequence of late-stage disease, but rather an early event that may explain pathology found in middle-aged people before cognitive decline.” , the authors explained in their article.
In addition, a compound formulated by the company called COR388, was shown in experiments with mice that it could reduce the bacterial load from a set level. P. gingivalis brain infection, while reducing the production of beta-amyloid and neuroinflammation.
We’ll have to wait and see what future research uncovers about this link, but the research community is cautiously optimistic.
“Until now, drugs that target toxic proteins in bacteria have only shown benefit in mice, but with no new dementia treatments in more than 15 years, it’s important that we try as many approaches as possible to address diseases like Alzheimer’s,” said Alzheimer’s Chief Scientific Officer David Reynolds. Research commented in a statement.
The findings were reported in Progress of science.
An earlier version of this story was first published in January 2019.