Alzheimer’s disease is the most common cause of dementia in the UK, according to the NHS. Although its exact cause remains unclear, medical experts have identified several risk factors, including advancing age, untreated depression, a family history of the condition, and lifestyle factors linked to cardiovascular health.
In recent years, however, a growing body of scientific research has begun to challenge the traditional view of Alzheimer’s, suggesting it may not be solely a neurodegenerative disease but could also involve infection.
A study published in 2019 proposed a possible connection between Alzheimer’s and gum disease. The research, led by microbiologist Jan Potempa of the University of Louisville, detected the presence of Porphyromonas gingivalis—the bacterium responsible for chronic periodontitis—in the brains of people who had died with Alzheimer’s disease.
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| P. gingivalis’ gingipains (red) among neurons in the brain of a patient with Alzheimer’s. (Cortexyme) via sciencealert |
Earlier experiments conducted by Cortexyme, Inc. using mice found that oral infection with P. gingivalis resulted in increased production of beta-amyloid (Aβ), the sticky protein plaques commonly associated with Alzheimer’s, within the animals’ brains.
“Infectious agents have previously been linked to the development and progression of Alzheimer’s disease, but the evidence for causation has not been convincing,” explained Dr. Stephen Dominy, co-founder of Cortexyme.
Further analysis focused on gingipains, the toxic enzymes produced by P. gingivalis. Researchers found that elevated levels of these enzymes were associated with tau and ubiquitin—two proteins already known to play a role in Alzheimer’s pathology.
Notably, gingipains were also discovered in the brains of individuals who had never been diagnosed with Alzheimer’s. This raised an important question: did these individuals develop brain infection before symptoms emerged, or did cognitive decline later lead to poor oral health?
The researchers addressed this uncertainty in their paper, stating:
“Our identification of gingipain antigens in the brains of individuals with Alzheimer’s disease and also in those with Alzheimer’s pathology but no dementia diagnosis suggests that brain infection with P. gingivalis is not the result of poor dental care following cognitive decline. Instead, it appears to be an early event that may help explain pathological changes seen in middle-aged individuals prior to noticeable symptoms.”
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The mouse studies also revealed that a compound developed by Cortexyme, known as COR388, reduced both amyloid-beta production and neuroinflammation. Whether similar effects can be achieved in humans remains to be determined through further research.
“Drugs targeting the toxic proteins produced by this bacterium have so far only demonstrated benefits in animal studies,” said David Reynolds, Chief Scientific Officer at Alzheimer’s Research. “However, given that no new dementia treatments have emerged in over 15 years, it is vital that we explore every possible avenue in the fight against Alzheimer’s disease.”
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