Alzheimer’s disease is the most common cause of dementia in the UK, according to the NHS. Its exact cause is still not fully understood, though clinicians point to a range of possible contributing factors, including advancing age, untreated depression, family history, and lifestyle-related risks—particularly conditions linked to cardiovascular health.
In recent years, however, a growing number of studies have strengthened a controversial idea: that Alzheimer’s may not only be a disease process, but could also involve an infectious component.
One widely discussed line of research came in 2019, when a study suggested a possible connection between Alzheimer’s and gum disease.
The research, led by senior author Jan Potempa, a microbiologist at the University of Louisville, reported that Porphyromonas gingivalis—the bacterium associated with chronic periodontitis (gum disease)—was detected in the brains of people who had died with Alzheimer’s.
Earlier experiments in mice, conducted by Cortexyme, Inc., added to the interest. In those studies, oral infection with P. gingivalis was linked to increased production of beta-amyloid (Aβ)—the sticky protein deposits commonly associated with Alzheimer’s—in the animals’ brains.
“Infectious agents have been implicated in the development and progression of Alzheimer’s disease before, but the evidence of causation hasn’t been convincing,” said Dr. Stephen Dominy, Cortexyme co-founder.
Researchers also examined gingipains, toxic enzymes produced by P. gingivalis. They found that higher gingipain levels were associated with two other proteins already tied to Alzheimer’s development: tau and ubiquitin.
At the same time, the team also detected these toxic gingipains in the brains of deceased individuals who had never been diagnosed with Alzheimer’s. That finding raised a key question: were those individuals on a path toward Alzheimer’s and simply never lived long enough to be diagnosed, or did Alzheimer’s-related decline lead to poorer oral hygiene and greater vulnerability to gum infection?
Addressing that uncertainty, the authors argued that finding gingipain markers not only in diagnosed Alzheimer’s cases but also in individuals with Alzheimer’s-type brain pathology without a dementia diagnosis suggests the infection may occur earlier than symptoms. In their view, this supports the possibility that brain infection with P. gingivalis is not merely the result of late-stage disease or reduced dental care after dementia begins, but could be an early event that helps explain changes seen in middle-aged people before cognitive decline becomes obvious.
The mouse experiments also pointed to a potential therapeutic angle. They reported reduced amyloid-beta production and decreased neuroinflammation after treatment with a Cortexyme-developed compound known as COR388.
Whether the same effect would occur in humans remains unproven and requires further research.
As David Reynolds, chief scientific officer at Alzheimer’s Research, noted, treatments aimed at the bacteria’s toxic proteins have shown benefits so far only in mice. Still, with no major new dementia treatments in more than 15 years, he emphasized the importance of investigating as many promising approaches as possible in the search for effective Alzheimer’s therapies.
