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expert reaction to study looking at Alzheimer’s Disease and a bacterium that causes gum disease

Research published in Science Advances suggests a link between periodontitis and Alzheimer’s disease. Gingipain (toxic proteases from P. gingivalis) inhibitors may be used in treating P. gingivalis and neurodegeneration in Alzehimer’s disease.

Prof Clive Ballard, Medical School Pro-Vice-Chancellor, University of Exeter, said:

“The study further supports a key link between oral health and dementia, suggesting that it isn’t simply an association but highlights a potential mechanistic link that the bacteria may be directly acting on processes in the brain relevant to Alzheimer’s disease. But perhaps more importantly, this study highlights the importance of oral health, and that this should be a much higher public health priority, especially in older people.”

Dr James Pickett, Head of Research at Alzheimer’s Society, said:

“In research we’ve supported to uncover the key risk factors for Alzheimer’s disease, gum disease hasn’t emerged as a major cause for concern.

“This latest study found evidence of gum disease bacteria in the brains of people who died with Alzheimer’s, but also found that people who didn’t have Alzheimer’s showed some of these same signs. The laboratory work does suggest that this infection could cause damage to cells of the brain but there isn’t yet clear evidence that it can cause this damage in people or result in Alzheimer’s.

“Success of this new drug depends on whether the infection really does play an important role in Alzheimer’s disease – it’s important to pursue that as there hasn’t been a new drug for dementia in 15 years. The upcoming clinical trial will be a crucial test to see if this can be a potential treatment for Alzheimer’s.”

Prof Tiago Outeiro, Professor of Neurodegeneration, Newcastle University, said:

“Humans carry more bacterial cells in their body than their own human cells, so the contributions of the microbiome to health and disease need to be further investigated. In particular, the microbiome has received recent attention in the context of neurodegenerative diseases affecting the brain. Identifying microbes associated with disease is extremely attractive, as this might lead to the identification of strategies, such as antibiotics, which may specifically affect those microbes which associate with disease.

“In this context, the present study is particularly interesting, as it identifies a common pathogen and suggests it may play a role in Alzheimer’s Disease. One question that will require a lot of additional work is whether this pathogen is specific for Alzheimer’s Disease, or whether it is a signal of more general alterations taking place during neurodegeneration.”

Professor Tara Spires-Jones, UK Dementia Research Institute Programme Lead and Deputy Director, Centre for Discovery Brain Sciences, University of Edinburgh, said:

“Researchers from the company Cortexyme have published a study potentially linking a bacteria called Porphyromonas gingivalis (Pg) that causes gum disease with Alzheimer’s disease.  Stephen Dominy and team examined brain tissue from people with Alzheimer’s disease and healthy control subjects and detected evidence of this Pg bacteria in almost every person they examined, regardless of whether they had Alzheimer’s.  While the levels of the bacteria itself do not seem different in Alzheimer’s patients compared to healthy controls (with small numbers examined, 3 Alzhiemer’s patients and 6 controls), a larger experiment looking at proteins produced by these bacteria (of around 100 people) showed an increase in bacterial proteins in Alzheimer’s cases compared to controls.  In mice, treatment with the company’s experimental drug reduces the increases of an Alzheimer’s related protein when the mice were infected with Pg bacteria.

“It is worth noting that Pg bacterial proteins were found in healthy people and some people with Alzheimer’s disease did not have increased levels compared to these controls.  People with Alzheimer’s disease also have disruption of their blood brain barrier, making them more susceptible to getting infections in their brains, so while these data are interesting, it is possible that the infection is a by-product instead of a cause of disease.  The data from mice in this paper show small increases in the levels of one of the Alzheimer’s associated proteins with Pg infection that were prevented with the experimental drug, but these mice did not develop any Alzheimer’s pathology and were conducted in small groups (around 10 mice per group).  So it’s great news that a recent trial by this company showed this drug is safe in people and this study provides some evidence that it may affect Alzheimer’s related proteins; however, we will have to await the larger clinical trial to see if it will be beneficial to people living with Alzheimer’s disease.”

Dr David Reynolds, Chief Scientific Officer from Alzheimer’s Research UK, said:

“Previously the P. gingivalis bacteria associated with gum disease has been found in the brains of people with Alzheimer’s but it remains unclear what role, if any, it plays in the development of the disease. In this well-conducted study, researchers were able to show that when genetically modified mice were given P. gingivalis, the bacteria was found in the brain alongside higher levels of the hallmark Alzheimer’s protein, amyloid.

“While some studies have found higher levels of bacteria in the brain during Alzheimer’s, it has been difficult to tell if they have played a direct role in the development of the disease.

“We know diseases like Alzheimer’s are complex and have several different causes, but strong genetic evidence indicates that factors other than bacterial infections are central to the development of Alzheimer’s, so these new findings need to be taken in the context of this existing research.

“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.

“Drugs targeting the bacteria’s toxic proteins have so far only shown benefit in mice, yet with no new dementia treatments in over 15 years it’s important that we test as many approaches as possible to tackle diseases like Alzheimer’s. It’s important we carefully assess all new potential treatments, and this drug is currently in an early phase clinical trial to establish if it is safe for people. We will have to see the outcome of this ongoing trial before we know more about its potential as a treatment for Alzheimer’s.”

‘Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors’ by Stephen Dominy et al. was published in Science Advances at 19:00 UK time on Wednesday 23rd January

All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/tag/dementia/

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