How a Common Mouth Bug Might Spark Alzheimer’s Disease

From Dental Plaque to Brain Plaques: The Alzheimer’s Connection (Part 1 of 4 in the series: The Plaque-Making Bacteria That Could Be Driving Alzheimer’s)

When most people think of Alzheimer’s disease, they picture the brain: memory loss, confusion, and changes in personality that come with progressive damage to neurons. But what if part of the story begins not in the brain, but in the mouth?

Over the last decade, researchers have discovered something astonishing. In autopsy samples of people who died with Alzheimer’s disease, scientists found DNA and toxic proteins from a common oral bacterium, Porphyromonas gingivalis, a plaque-forming pathogen known for driving periodontitis.^{1, 5}

This discovery has shifted how we think about Alzheimer’s. Instead of being a single, uniform disease, Alzheimer’s may actually have multiple pathways, and in some cases the trail of clues leads straight back to dental plaque. Research continues to accumulate, from basic science to animal studies, adding evidence to this intriguing connection. ^{4, 5, 6}

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What They Found in the Brain

The link between plaque-forming bacteria and Alzheimer’s began with forensic-style science: looking carefully at the brains of patients after death. What researchers uncovered was striking. DNA fragments from P. gingivalis were repeatedly detected in brain tissue, along with its virulence factors known as “gingipains”.^{1, 5}

These enzymes are harmful. In laboratory studies, gingipains were shown to spark brain inflammation and accelerate the buildup of amyloid-beta, the sticky protein that clumps into plaques in Alzheimer’s disease. ^{1, 5}

Multiple groups have since confirmed traces of oral bacteria or gingipains inside the brain. It was as if the microbes had left fingerprints at the crime scene.^{3, 8}

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Meet the Culprit: Porphyromonas gingivalis

So, what exactly is this bacterium that keeps appearing in Alzheimer’s brains?

P. gingivalis is a plaque-forming bacterium best known for driving periodontitis, a chronic inflammatory condition of the gums. Areas of dental plaque and inflammation provide the ideal environment for this bacterium to flourish.

It does not normally cause disease beyond the mouth, but when dental plaque accumulation persists, it can spread and drive inflammation. Over time, it damages the gums, loosens teeth, and provides opportunities to enter the bloodstream. ^9,10,11

Researchers have identified seven key ways this mouth bacterium may harm the brain:

1. Toxic enzymes (gingipains) – These molecular “scissors” can damage neurons and structural proteins, and are linked to amyloid accumulation.^{1, 4, 5, 6}

2. Over-activating the brain’s immune cells (inflammation) – Microglia respond to bacterial components with inflammation that can harm nearby neurons.^{1, 4, 5, 6, 8}

3. Stealth nanocarriers (tiny toxin-filled packets) – Even without whole bacteria entering the brain, P. gingivalis releases tiny packages of toxins that can slip through protective barriers and trigger inflammation.^{4, 6, 13, 14}

4. Weakening the blood–brain barrier – Chronic infection may make the brain’s protective wall leakier, allowing harmful molecules to enter more easily.^1,6,7,8

5. Triggering excess amyloid-beta production – The brain may produce extra amyloid-beta in response to bacterial invaders, which can backfire and contribute to plaque buildup over time.^{1, 3, 5, 8}

6. Animal model evidence (transgenic mice and others) – Repeated exposure to P. gingivalis or its components causes amyloid buildup, tau pathology, neurodegeneration, and memory deficits in several animal models.¹⁴

7. Population-level associations – Observational studies show a link between long-term periodontitis and elevated Alzheimer’s risk, lending epidemiological support to the laboratory findings.^{4, 5, 6, 8, 14}

(For those who want to dive deeper into the science behind each mechanism, we will explore them in a future article.)

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A Mystery We Will Return To

How does a mouth bacterium end up in the brain at all? That is still being studied. Scientists suspect several routes: through inflamed gums into the blood, through nerve pathways linking the face and brain, or through a weakening blood–brain barrier as we age.^{7, 9, 11}

The truth is, we do not fully know yet. Scientists are still piecing the puzzle together, and it is such a fascinating question that deserves its own deep dive. We will explore this in Part 2 of the series.

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Why This Matters for Alzheimer’s

The big picture is this: P. gingivalis and its toxins may be capable of nudging the brain toward Alzheimer’s-like changes. In mice, oral infection led to amyloid buildup and memory problems.¹⁴ In human brains, the bacterial toxins have been linked with disease severity.¹

For decades, Alzheimer’s research has focused heavily on amyloid plaques and tangles as the primary causes. The bacteria story does not replace that theory, but it suggests a possible trigger, an upstream actor that might spark those destructive processes in some people.

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A Glimpse of a Drug That Almost Worked

This connection became strong enough that scientists developed a gingipain-blocking drug, COR388 (atuzaginstat). The idea was simple: stop the gingipains, stop the damage.

Early results were promising, but the trial was halted due to safety issues. The details and the lessons learned are worth unpacking. We will explore them in Part 3 of this series.

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Take-Home Message: Teeth and Brain, Connected

Alzheimer’s is not one disease. There are many biological routes that can lead to memory loss and brain decline. For some people, plaque-forming bacteria like P. gingivalis may be one of those routes.

The hopeful part is that unlike genes or age, oral hygiene is something we can control. Brushing, flossing, and regular dental check-ups may not just protect your smile, they may also help your memory stay sharp in the years ahead.

So the next time you reach for your toothbrush, remember you are not only protecting your teeth. You might also be protecting your mind, giving your memory a better chance at staying strong.

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References

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