Gum disease linked to Alzheimer's, study claimsPosted by Olderiswiser Editorial
"Gum disease bug could play 'central role' in development of Alzheimer's," The Independent reported. Here, Behind the Headlines news analysis service examines the science behind the story.
"Gum disease bug could play 'central role' in development of Alzheimer's," The Independent reports.
The causes of Alzheimer's disease are still debated. Most scientists think it is likely to be down to a combination of factors, including your genes and lifestyle.
But some believe it may be caused by an infectious disease and have been investigating bacteria called porphyromonas gingivalis (P. gingivalis) which is known to trigger gum disease (gingivitis).
Doctors have observed that gingivitis is more common among people with Alzheimer's disease, although that could be because these people find dental hygiene more challenging.
A team of researchers has found that proteins produced by P. gingivalis are present in higher concentrations in the brains of people with Alzheimer's disease.
In experiments on mice, they found that mice infected by mouth with P. gingivalis later showed signs of brain infection and deterioration; signs similar to those found in humans with early-stage dementia. They went on to find that a newly developed drug could clear the bacterial infection and seemed to stop brain deterioration. The new drug is now being tested on people in clinical trials.
While any advance in treatment of Alzheimer's disease is welcome, this research is at a very early stage. We don't know for sure that P. gingivalis causes Alzheimer's disease in humans, or that the drug will work.
Where did the story come from?
The researchers who carried out the study mostly worked at Cortexyme, a private biotech company, with others working at Jagiellonian University in Poland, the University of California, University of Louisville School of Dentistry and Harvard University School of Dental Medicine in the US, the University of Melbourne in Australia, and University of Auckland in New Zealand. The study was funded by Cortexyme, which was founded by some of the researchers involved in the study.
The UK media's reporting of the study was accurate and included some useful independent expert commentary.
What kind of research was this?
This study involved a series of experiments on human brain tissues in the laboratory and on mice. These types of experiments are useful in early studies exploring the disease process. However, looking at the presence of bacteria in human brain tissue doesn't tell us anything about whether this may have a role in causing the disease. Also we don't know that findings in mice will apply to humans.
What did the research involve?
Firstly, researchers looked at post-mortem brain tissue samples from around 100 people with and without Alzheimer's disease. They tested the tissue samples for the presence of 2 protein fragments produced by P. gingivalis bacteria, called gingipains to see if people with Alzheimer's disease had more gingipains in their brain tissue.
They tested the saliva and cerebrospinal fluid (CSF), which surrounds the brain and spinal cord, of people with Alzheimer's disease, looking for presence of P. gingivalis DNA.
They also ran an experiment where cultured cells grown in the laboratory were infected with P. gingivalis to see what effect that had on tau protein, a protein that forms tangles in the brains of people with Alzheimer's disease. They then developed a group of substances designed to block (inhibit) the action of gingipain and tested them on cells in the laboratory.
Experiments on mice included:
- checking whether infection of 8 mice with P. gingivalis through the mouth over 6 weeks would result in the bacteria showing up in the brain
- giving mice a substance that inhibits gingipains, to see if it could treat gingipain infection in mice, and how that compared to treatment with an antibiotic used to treat gingivitis
What were the basic results?
Researchers found gingipains in 91% and 96% (for each of the 2 protein types) of brain tissue samples from people with Alzheimer's disease compared to 39% and 52% of brain samples from people without Alzheimer's disease. They said the concentration of gingipains in brain tissue was "significantly higher" in brain samples from people with Alzheimer's disease.
They found P. gingivalis DNA in 7 out of 10 cerebrospinal fluid samples of people with Alzheimer's disease and all 10 matched saliva samples.
In laboratory experiments, they found cell cultures infected with P. gingivalis showed signs of fractured or broken-up tau protein.
Of the 8 mice infected with P. gingivalis through the mouth, all showed signs of brain infection after 6 weeks. Giving mice a gingipain-inhibiting substance by mouth twice a day treated the brain infection and was better at reducing bacterial load than the antibiotic moxifloxacin (a recommended treatment for people with gingivitis).
How did the researchers interpret the results?
The researchers say: "The findings of this study offer evidence that P. gingivalis and gingipains in the brain play a central role in the [disease development] of [Alzheimer’s disease]."
They add: "We also demonstrated [in living animals] that an orally-administered [gingipain] inhibitor is more effective than a high-dose subcutaneous broad spectrum antibiotic in clearing P. gingivalis from the brain."
This study presents new information about the possible link that a common mouth bacterium could have with Alzheimer's disease, and investigates a potential treatment. However, the mechanisms around the development of Alzheimer's disease are complex. We don't yet know how all the risk factors associated with the disease (such as age and lifestyle) and disease features (such as the presence of amyloid beta plaques and tau protein tangles) all fit together.
The study suggests that infection may be part of the picture. But it only shows an association, it still doesn't prove a causal link. It's worth noting that not all people with Alzheimer's had P. gingivalis in their cerebrospinal fluid – and there was no comparison group without Alzheimer's. Healthy individuals could also show P. gingivalis DNA in their CSF. After all, signs of P. gingivalis were found in up to half the brain tissue samples of people without the disease.
There is a long way to go to prove this is the answer – and even then it may only be a partial answer.
The researchers say they have also begun "new drug application-enabling studies" with the gingipain-inhibiting substance tested here. It is encouraging to hear that clinical trials are underway, but many drugs which seem promising at first for Alzheimer's disease do not turn out to be safe or effective in human trials.
Whether there is a link to Alzheimer's disease or not, good oral hygiene keeps teeth and gums healthy. Find out more about oral hygiene.
Analysis by Bazian | Edited by NHS Website
Links to the headlines
The Independent, January 24 2019
Mail Online, January 24 2019
Links to the science
Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitorsScience Advances. Published online January 23 2019
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