A landmark study published in Science Advances has found evidence suggesting that the bacterium responsible for gum disease, called Porphyromonas gingivalis, may play a role in the development of Alzheimer’s disease.
There have been previous hints from animal studies that this common oral bacteria may be linked in some way to Alzheimer’s disease. Work in mice has shown that P. gingivalis can cause damage to neurons and create inflammation like that seen in Alzheimer’s patients, and may be able to invade parts of the brain affected by the condition. Now, for the first time, researchers have found evidence of P. gingivalis in the brain tissue of human Alzheimer’s patients.
The scientists in the study analysed 54 samples of patient brain tissue taken from the hippocampus, an area of the brain that is responsible for the formation and storage of memories. In almost all of these samples, the researchers saw enzymes that had been released by P. gingivalis, called gingipains, and in some samples, they observed DNA from the bacterium itself. Moreover, higher levels of gingipains were found in the tissue that had more tau, a protein that has long been thought to play a role in Alzheimer’s disease.
The neural degeneration seen in Alzheimer’s is often associated with a build-up of two proteins: amyloid-beta and tau. These proteins accumulate to form sticky plaques in the brains of patients, and it‘s these plaques that have predominantly been the focus of strategies to treat the disease. Unfortunately, these efforts have so far been fruitless, and a clinical review from 2018 reported that the failure rate of drug development for Alzheimer’s is currently 99 per cent.
Although the field has suffered many years of setbacks, new ideas are now beginning to emerge, and some researchers have begun to think differently about the disease. In 2016, one group found evidence that amyloid plaques have antibacterial properties, and can develop in the brain in response to infection, potentially acting as a kind of sticky tangled mesh to trap pathogens. This finding, among others, has led some scientists to consider an infectious origin to the disease, such as a virus, fungus or bacteria. P. gingivalis may be an interesting contender.
Interpreting cause-and-effect can often be a tricky matter in these types of studies. In this case, researchers were aware of the possibility that the increased bacteria in the Alzheimer’s patient brains could be explained by poor oral hygiene because of the debilitating effect of the disease, rather than a root cause. To address this, they performed some follow-up studies, which they believe make a case for P. gingivalis as a causative factor in Alzheimer’s disease. In these experiments, mice were fed the bacteria, and developed symptoms similar to Alzheimer’s in humans. When they were given a drug to target the bacteria, the symptoms lessened.
Though intriguing, the study has limitations, and there is still a lot of work to be done before all the complexities of Alzheimer’s disease can be disentangled. Limited access to human brain tissue means that the study, like a lot of research in this area, is relatively small, and we will have to wait for results from large-scale clinical trials before any robust conclusions can be drawn.
Dr David Reynolds, of Alzheimer’s Research UK, emphasises the need to keep in mind the wider picture. “Maintaining good dental health is an important part of a healthy lifestyle, and while we don’t yet fully know the extent to which it can affect our dementia risk, the presence of a single type of bacteria is extremely unlikely to be the only cause of the condition.”
Dr Rudolph Tanzi, an Alzheimer’s researcher at Massachusetts general hospital, also urges caution. “It’s way too early to say that this result is valid. We need to see many more samples. We need much more replication.”
The findings have led to the development of a new drug, COR388, which aims to combat the disease via P. gingivalis. The drug is set to be tested in clinical trials later this year, and hopefully, then we will know more about its potential as a treatment option.
For now, Alzheimer’s disease is still impacting many lives, and a new drug for the condition has not been developed in 15 years. These findings bring a novel perspective and hope to allow the exploration of new therapies to treat this prevalent condition.
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