The Cause of Alzheimer's Disease Could Come From Inside Your Mouth

The Cause of Alzheimer’s Disease Could Come From Inside Your Mouth

In recent years, a growing number of scientific studies have supported an alarming hypothesis: Alzheimer’s disease is not just a disease, it is 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 goes far beyond what we used to think.

One such study, published in 2019, suggested what may be one of the most definitive leads yet for a bacterial culprit behind Alzheimer’s disease, and it comes from a somewhat unexpected quarter: the disease. gums.

In a paper led by lead author Jan Potempa, a microbiologist from the University of Louisville, researchers reported the discovery of Porphyromonas gingivalis – the pathogen responsible for chronic periodontitis (gum disease) – in the brains of patients who died of Alzheimer’s disease.

530 alzheimer's gum disease bacteria 1P. gingivalis gingipains (red) among neurons in the brain of a patient with Alzheimer’s disease. (Cortexym)

It wasn’t the first time the two factors were linked, but the researchers went further.

In separate experiments with mice, oral infection with the pathogen resulted in colonization of the brain by the bacteria, as well as increased production of beta-amyloid (Aβ), the sticky proteins commonly associated with Alzheimer’s disease. Alzheimers.

The research team, coordinated by pharmaceutical startup Cortexyme, which was co-founded by first author Stephen Dominy, did not claim to have found definitive evidence for the causation of Alzheimer’s disease.

But it was clear they thought we had a strong investigative lead here.

“Infectious agents have previously been implicated in the development and progression of Alzheimer’s disease, but the evidence for causation has not been convincing,” Dominy said at the time.

“Now, for the first time, we have strong evidence linking the intracellular pathogen to Gram-negative, P. gingivalisand the pathogenesis of Alzheimer’s disease. »

Additionally, the team identified toxic enzymes called gingipains secreted by bacteria in the brains of Alzheimer’s patients, which correlated with two distinct markers of the disease: tau protein and a protein tag called ubiquitin.

But even more compelling, the team identified these toxic gingipains in the brains of deceased people who were never diagnosed with Alzheimer’s disease.

This is important, because even if P. gingivalis and the disease have been linked before, it’s never been known – to put it simply – if gum disease causes Alzheimer’s disease or if dementia leads to poor oral care.

The fact that low levels of gingipains were evident even in people who had never been diagnosed with Alzheimer’s disease could be compelling evidence – suggesting that they might have developed the disease had they lived longer.

“Our identification of gingipain antigens in the brains of individuals with Alzheimer’s disease and also Alzheimer’s disease pathology, but no diagnosis of dementia argues that brain infection with P. gingivalis is not the result of poor dental care following the onset of dementia or a consequence of advanced disease, but is an early event that may explain the pathology found in people of age mean before cognitive decline,” the authors explain in their paper.

Additionally, a compound formulated by the company, called COR388, has been shown in mouse experiments to reduce the bacterial load of an established organism. P. gingivalis brain infection, while reducing beta-amyloid production and neuroinflammation.

We’ll have to wait and see what future research uncovers on this link, but the research community is cautiously optimistic.

“Drugs targeting the bacteria’s toxic proteins have so far only shown benefit in mice, but without new dementia treatments for more than 15 years, it’s important that we test as many approaches as possible. to fight diseases like Alzheimer’s,” said Alzheimer’s Scientific Director David Reynolds. Research commented in a press release.

The findings were reported in Scientists progress.

An earlier version of this story was first published in January 2019.

#Alzheimers #Disease #Mouth

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