Common gum disease plays a ‘central role’ in Alzheimer’s development Porphyromonas gingivalis has been found in the brains of people with Alzheimer’s but it remains unclear what role it plays in the disease.

A common gum disease bug plays a “central role” in the development of Alzheimer’s, according to scientists who say they have finally found “solid evidence” linking the bacteria to dementia.

Porphyromonas gingivalis (Pg) is one of the main causes of gum disease and tooth loss and has also been associated with artery damage. The Pg bacteria has been found in the brains of people with Alzheimer’s but experts say it remains unclear what role, if any, it plays in the development of the disease.

The latest study by a US-led international team of scientists appears to put the link beyond question – and potentially transform current thinking about how Alzheimer’s disease should be tackled.

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Researchers were able to show that when genetically modified mice were given Pg, the bacteria was found in the brain alongside higher levels of the protein amyloid, a hallmark of Alzheimer’s.

They made the discovery after analysing brain tissue, spinal fluid, and saliva from dead and living patients with diagnosed and suspected Alzheimer’s. They found evidence of toxic enzymes, known as gingipains, that are released by Pg, as well as DNA from the bacterium. In addition, the bug was found to spread from the mouths to the brains of mice. Tests on the animals confirmed that gingipain enzymes destroyed brain neurons.

The scientists tested drugs that blocked gingipains and found they were able halt the neurodegeneration. One drug, given to mice in food, effectively treated Pg brain infections and prevented the loss of memory neurons. The team has now developed a new drug, COR388, that better penetrates the central nervous system and could form the basis of a human Alzheimer’s treatment. A large-scale clinical trial that will involve giving the drug to patients with mild to moderate Alzheimer’s is planned for later this year.

New drug?

Dr Stephen Dominy, one of the study authors and co-founder of the US company Cortexyme, which developed COR388, said: “Now, for the first time, we have solid evidence connecting the intracellular gram-negative pathogen Pg and Alzheimer’s pathogenisis, while also demonstrating the potential for a class of small molecule therapies to change the trajectory of the disease.”

The findings are published in the latest edition of the journal Science Advances.

The scientists tested more than 50 brain tissue samples and found that 96 per cent contained one type of gingipain enzyme and 91 per cent another. The mouse studies found that blocking gingipains effectively protected the hippocampus, a part of the brain vital to memory, from Pg infection. It also reduced inflammation and levels of beta-amyloid.

Writing in the journal, the scientists concluded: “The findings of this study offer evidence that P. gingivalis and gingipains in the brain play a central role in the pathogenesis (development) of AD (Alzheimer’s disease), providing a new conceptual framework for disease treatment.”

How to avoid gum disease Gum disease affects an estimated 45 per cent of the UK adult population, according to the British Dental Association. It’s much less common in children. Mild cases of gum disease can usually be treated by maintaining a good level of oral hygiene. This includes brushing your teeth at least twice a day and flossing regularly. You should also make sure you attend regular dental check-ups. In most cases, your dentist or dental hygienist will be able to give your teeth a thorough clean and remove any hardened plaque.

The bacteria may access the brain by infecting immune system cells or spreading through cranial nerves passing through the head and jaw, said the researchers. Laboratory tests indicated that gingipain enzymes may trigger tau tangles – knots of proteins within neurons that are thought to drive the damage caused by Alzheimer’s.

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Commenting on the study, Professor Clive Ballard, from the 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.”

No clear evidence

Dr James Pickett, head of research at Alzheimer’s Society, said: “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.”

Professor Tara Spires-Jones, deputy director at the University of Edinburgh’s Centre for Discovery Brain Sciences, said it was “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”.

She added: “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.”