Research just published presents evidence of a causal link between the microbe causing common gum disease and Alzheimer’s. This exciting discovery opens up the possibility of dementia prevention and treatment in totally unexpected ways. There may be a powerful preventative tool in every bathroom!
As a former Bacteriologist I and many in the medical scientific community have become very excited by research published in the respected, peer reviewed, scientific journal Science Advances on 23rd Jan. 2019 (link to original paper is here).
The research presents evidence that the common gum disease bacterium P. gingivalis may be involved in causing Alzheimer’s disease and proposes an approach to treating the disease that attacks the neuron damaging proteins produced by the microbe.
We always have to be cautious about giving too much credence to ‘miracle cures’ until they have been repeated by other scientists and proven in large scale human trials but the results of this piece of work come very close to fulfilling Koch’s postulates – a set of criteria acknowledged by medical scientists as necessary to prove that a microbe is the cause of a particular disease (Robert Koch formulated the germ theory of disease).
If confirmed this would not be the first time we have had to throw away previous ideas about the causes of a commonly occurring disease. I remember many years ago when I lived in Tokyo, one of my colleagues was diagnosed with a stomach ulcer. He was told that this was probably caused by stress or diet (or both) and needed to find ways to modify his lifestyle (difficult if you are a businessman in Japan!) and take medications to reduce his stomach acid. A few years later the Australian doctor Barry Marshall discovered that stomach ulcers were caused by the bacterium Helicobacter pylori (and received a Nobel prize for his work). This led to a totally different approach to treatment.
Alzheimer’s disease has for many years been associated with the increased incidence of two proteins in the brain called amyloid and tau (the so called ‘sticky plaques’). It was thought (as with high stomach acid and ulcers) that these proteins may in some way be ‘causing’ dementia and much research has been put into trying to find ways of reducing the presence of these proteins in the brain. To date this approach has not been very successful.
What if these proteins, rather than causing Alzheimer’s, are actually the body’s way of fighting off a harmful bacterial infection? In fact such plaques have been found in the brains of people in their 90s with no sign of dementia! In 2016 scientists did indeed discover that the amyloid protein seems to be produced by cells as a sticky defence against bacteria.
A important clue connecting gum disease with Alzheimer’s came in research published in the BMJ Journal of Neurology, Neurosurgery & Psychiatry (28th Oct 2009 link to paper is here). In this J.M.Nobel and coworkers found that levels of a periodontis (gum disease) were linked to the impaired delayed memory and impaired calculation symptoms typical of dementia. At that time it wasn’t clear if the damaged brain was allowing the microbes to invade it or whether the bugs were actually causing the brain damage (the two were linked – but which one was the cause?).
At this point several research teams started to focus more on the relationship between gum disease microbe P. gingivalis and Alzheimer’s disease. Mice, genetically engineered to develop Alzheimer’s were found to have increased Alzheimer’s symptoms following infection with the gum disease microbe. P. gingivalis has also been found to invade and cause inflamation in the brain regions affected by Alzheimer’s in humans. The microbe can also lead to typical Alzheimer’s brain inflation, neuron (brain nerve cell) damage and amyloid protein plaques in healthy mice.
In the latest research (published on 23rd Jan 2019) two poisonous proteins which P. gingivalis uses to ‘eat’ human tissues were found in 99 and 96% of human brain samples from 54 Alzheimer’s patients’ hippocampus (the part of the brain involved in memory). These bacterial poisons are called gingipains and were also found in parts of the brain producing high levels of the alzheimer’s tau protein (and thus also linked to cognitive decline).
This team also looked for, and found, P. gingivalis DNA in the part of the brain involved in conceptual thinking, the cerebral cortex, in the brains of three Alzheimer’s patients.
A unique feature of this report is that it demonstrated the presence of the common gum disease bacterium DNA in human brains and it showed that the bacterial poisons (gingipains) were in the same location as the plaques typically associated with Alzheimer’s.
One thing that makes the team confident P. gingivalis may be the ‘cause‘ of Alzheimer’s rather than its ‘result‘ relates to the fact that some people with no symptoms of dementia can have small levels of P. gingivalis as well as plaque proteins in their brain. This indicates that the microbes are invading the brain before symptoms of Alzheimer’s become apparent – it is known that the plaque proteins (amyloid and tau) can accumulate in the brain for 10-20 years before external symptoms of dementia appear.
More evidence that the gum disease bacteria actually ’cause’ Alzheimer’s came from studies in which mice were given P. gingivalis. This lead to brain infection by the bacterium, production of the amyloid protein, tangling of tau proteins (= plaques) and brain cell (neuron) damage in those areas normally affected by Alzheimer’s.
More work is needed to determine how P. gingivalis gets into the brain. If dental plaque is allowed to build up underneath your gums localised areas of inflammation can build up where the microbe thrives and releases its poisonous tissue destroying proteins (= bad breath!). Interestingly people with fewer teeth (a symptom of chronic periodontitis) are also more likely to have dementia.
As the P. gingivalis destroys the tissues around the inflamed gums it can enter the blood stream and get to other parts of the body. It may also enter the blood if the gums are damaged through disease, eating or incorrect brushing. Although typically the blood brain barrier protects us from microbes entering the brain we know that P. gingivalis can get inside white blood cells and the cells lining blood vessels. This could be how it can get into the brain. Another route to the brain may be via nerve cells near the mouth – the microbes could travel along these nerve highways into the brain.
Once it is in the brain there are two possible ways these bacteria can cause damage. On the one hand they may encourage the production of high amounts of amyloid – the body’s defence against bacterial attack – which then leads to inflammatory damage by the immune system. Alternatively the microbe could use its gingipain proteins to damage brain tissues in the same way it destroys tissues elsewhere in the body. The kind of inflammation in your gums might also be taking place in your brain!
If it is confirmed that this is a cause of Alzheimer’s disease (there could well be more than one cause) it opens up some interesting possibilities regarding prevention and treatment. Not everyone develops gum disease (good dental hygiene is key here) and not everyone with gum disease develops dementia – so presumably the actual level of damage/inflammation could play a key role. Also genetic factors will influence a person’s susceptibility to the progression of the disease
We can expect a lot of research to now be undertaken into how the brain can be helped to defend itself against Porphyromonas gingivalis infections. These bacteria can develop antibiotic resistance (not surprising as they live in the cavity into which we pour most of our antibiotic prescriptions!) so this approach may be limited in effectiveness. One exciting area of research could be aimed at attacking the bacterial toxins (the gingipains) which are known to attack a particular amino acid in the immune system’s defence protein ApoE (patients with a mutant of ApoE having an excess of this amino acid are more susceptible to Alzheimer’s).
I. for one, will be turning up with increased enthusiasm at my 6 monthly appointment with the dental hygienist next week!
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