Growing evidence suggests Alzheimer’s disease might not be solely a disorder of aging neurons but could also involve an infectious process. While the exact mechanisms remain under investigation, recent studies indicate that the origins of the disease may extend far beyond the brain.
One 2019 study provided one of the strongest clues yet, pointing to a surprising potential source: gum disease. The research team, led by microbiologist Jan Potempa of the University of Louisville, reported finding Porphyromonas gingivalis—the bacterium responsible for chronic periodontitis—in the brain tissue of deceased Alzheimer’s patients.
Previous studies had hinted at a link between gum disease and Alzheimer’s. But this work went further. In mouse experiments, oral infection with P. gingivalis resulted in bacterial colonization of the brain and increased production of amyloid-beta, the protein that forms the disease’s characteristic plaques.
The study was coordinated by Cortexyme, a pharmaceutical startup co-founded by first author Stephen Dominy. The researchers did not claim to have identified a definitive cause of Alzheimer’s, but they argued that the findings strengthen the case for a bacterial role in its development.
“Infectious agents have been implicated in Alzheimer’s before, but the evidence for causation hasn’t been convincing,” Dominy said at the time. “Now we have solid evidence connecting P. gingivalis to Alzheimer’s pathogenesis.”
The team also detected toxic enzymes called gingipains—produced by the bacteria—in the brains of Alzheimer’s patients. These enzymes correlated with levels of tau and ubiquitin, two established markers of the disease.
More strikingly, low levels of gingipains were found in people who had no clinical diagnosis of Alzheimer’s but showed early signs of its pathology. This supports the idea that gum infection may precede cognitive decline rather than result from it.
“Our identification of gingipain antigens in people with and without dementia suggests brain infection with P. gingivalis is an early event,” the authors wrote. “It could help explain Alzheimer’s-related changes in middle age, before symptoms appear.”
The researchers also tested an experimental drug, COR388, which reduced bacterial levels, amyloid-beta production, and inflammation in mice with established brain infections.
Although more research is needed, the findings have been met with cautious optimism. Alzheimer’s remains the most common form of dementia and one of the leading causes of death in the United States, yet its origins and triggers remain unclear.
Risk factors appear to be shifting as well. In 2011, physical inactivity was considered the most significant modifiable risk factor. By 2022, obesity had overtaken it, according to a large cross-sectional study.
“It’s important that we test as many approaches as possible to tackle diseases like Alzheimer’s,” said David Reynolds, chief scientific officer at Alzheimer’s Research.
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