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Gum disease may be central to Alzheimer's development, say scientists
Gum disease may play a pivotal role in the development of Alzheimer’s disease, scientists believe, leading to hopes that good dental care or drugs could stave off or halt dementia.
Researchers said they now had ‘solid evidence’ that the bacteria which causes periodontitis produces an enzyme which destroys neurons leading to memory loss.
The bacteria Porphyromonas gingivalis ( P. gingivalis) is one of the chief causes of gum disease and tooth loss in humans, and has previously been associated with heart problems.
In a series of experiments, an international team of researchers tested the brains of 53 people with Alzheimer’s and found the bacteria enzyme in 96 per cent.
DNA evidence of the bacteria was also found in spinal fluid from seven out of 10 living patients diagnosed with Alzheimer's, and it was also present in the saliva of each one.
In animal studies the bug was also found to spread from the mouths of mice to their brains, where the enzyme destroyed neurons.
The researchers believe that the bacteria may be responsible for the tell-tale tangles of tau proteins seen in the brains of Alzheimer’s patients which contribute to the death of brain cells.
Writing in the journal Science Advances, they said: “After entering the brain, we suggest that P. gingivalis may spread slowly over many years from neuron to neuron along anatomically connected pathways.
“We propose that tau pathology seen in Alzheimer’s disease brains may be due to the spread of P. gingivalis.”
Gum disease affects an estimated 45 per cent of the UK population, according to the British Dental Association (BDA), and nearly 10 per cent suffer from the more severe form of periodontitis.
The scientists also tested drugs which blocked the enzyme produced by bacteria and found they were able to half brain degeneration in mice.
One drug, given to mice in food, effectively treated P. gingivalis brain infections and prevented the loss of memory neurons. It also reduced inflammation and levels of beta-amyloid, a brain molecule strongly linked to Alzheimer's.
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.
Dr Stephen Dominy, one of the study authors and co-founder of the US company Cortexyme, which developed COR388, said: “Infectious agents have been implicated in the development and progression of Alzheimer's disease before, but the evidence of causation hasn't been convincing.
“Now, for the first time, we have solid evidence connecting the intracellular gram-negative pathogen Pg (P. gingivalis) and Alzheimer's pathogenisis, while also demonstrating the potential for a class of small molecule therapies to change the trajectory of the disease.”
Dr David Reynolds, chief scientific officer at charity Alzheimer's Research UK, said that Alzheimer's was likely to have multiple causes, one of which may be gum disease bacteria.
He added: “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."
BDA scientific adviser Professor Damien Walmsley said: “This study offers a welcome reminder that oral health can't remain an optional extra in our health service.
“Everyone's life can be improved by regular appointments and good oral hygiene, reducing the bacterial load that's ever present in our mouths to a level that's unlikely to cause tooth decay, gum disease or tooth loss.”
Dr James Pickett, Head of Research at Alzheimer’s Society, added: “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.”