Growing Evidence of Infection’s Role in Alzheimer’s Disease

In recent years, a number of scientific studies have supported a concerning hypothesis: Alzheimer’s disease may not just stem from the natural aging of the brain, but rather be linked to infections.

Researchers are still working on understanding the precise mechanisms behind this potential connection. However, various studies indicate that the emergence of Alzheimer’s could be more complex than previously thought.

A fascinating study from 2019 pointed towards a possible bacterial culprit related to Alzheimer’s, surprisingly from gum disease.

In this study led by Jan Potempa, a microbiologist at the University of Louisville, researchers found Porphyromonas gingivalis, the pathogen responsible for chronic periodontitis, in the brains of deceased Alzheimer’s patients.

This wasn’t the first time the two issues had been associated; however, the research team explored the connection further.

In experiments involving mice, they discovered that an oral infection with the pathogen resulted in bacteria colonizing the brain and increased production of amyloid beta (Aβ), the proteins often linked to Alzheimer’s.

The Cortexyme research team, co-founded by first author Stephen Dominy, didn’t claim to have showcased definitive proof of Alzheimer’s causation, but they seemed to regard their findings as remarkably significant.

“While infectious agents have been previously associated with Alzheimer’s development, convincing evidence of causation was lacking,” Dominy explained. “For the first time, we have tangible evidence linking the pathogen P. gingivalis to Alzheimer’s pathogenesis.”

Additionally, the researchers identified toxic enzymes called gingipains produced by this bacteria in the brains of Alzheimer’s patients, correlating with two separate disease markers: tau protein and ubiquitin.

Interestingly, they also found these toxic enzymes in the brains of individuals who had never been diagnosed with Alzheimer’s. This finding raises important questions: does gum disease lead to Alzheimer’s, or could dementia result in poorer oral hygiene?

The presence of lower levels of gingipains in those without Alzheimer’s might suggest they could have developed the condition if they had lived longer.

The authors stated that their findings indicate brain infection with P. gingivalis isn’t merely a result of deteriorating dental care as dementia progresses but could be an early event explaining pathology in middle-aged individuals prior to any cognitive decline.

Moreover, a compound developed by Cortexyme, named COR388, showed promise in mouse studies, demonstrating its potential to decrease the bacterial load in established P. gingivalis brain infections while also reducing amyloid-beta production and neuroinflammation.

While the community remains cautiously optimistic about the implications, more research will be needed to understand this link better.

Currently, Alzheimer’s remains the most prevalent form of dementia and a leading cause of death in the U.S. Despite extensive study, the origins and progression of the disease remain largely unknown.

Over the past decade, the primary risk factors for developing Alzheimer’s appear to have changed. A cross-sectional analysis from 2022 indicated that obesity has surpassed physical inactivity as the key modifiable risk factor for dementia.

David Reynolds, chief scientific officer from Alzheimer’s Research, emphasized, “It’s crucial we explore various approaches to address diseases like Alzheimer’s.”

The study findings were detailed in the journal Science Advances.

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