Monday, 19 August, 2019

Gum disease's 'central role' in Alzhemer's

A simple blood test could predict if a patient will develop Alzheimer's disease up to 16 years before symptoms begin a new study finds A simple blood test could predict if a patient will develop Alzheimer's disease up to 16 years before symptoms begin a new study finds
Anna Jefferson | 26 January, 2019, 05:14

Alzheimer's is a much-feared condition that, according to the Alzheimer's Association affected over 5.7 million people in the U.S. alone, in 2018.

She notes that good oral health could one day fall into one of these categories if there's more evidence to show that gum disease actually increases the risk for developing dementia.

Traces of the bacterium Porphyromonas gingivalis, which causes chronic gum disease, have been found in the brains of people who had Alzheimer's disease. Dominy agrees. 'Certainly, reducing the P. gingivalis load in the mouth, especially at an early age, should be taken more seriously than it now is based on our data, ' he says, though he adds that merely targeting gum disease is unlikely to help with infections of P. gingivalis in the brain.

The provocative findings are the latest in a wave of research suggesting microbial infections may play a role in Alzheimer's disease.

"We now have strong evidence connecting P. gingivalis and Alzheimer's pathogenesis, but more research needs to be done before P. gingivalis is explicitly implicated in the causation or morbidity of Alzheimer's disease", said study co-author Jan Potempa. At the time, he was treating people with HIV at the University of California, San Francisco.

The study, by USA company Cortexyme, says P.?gingivalis plays a "central role" in the development of Alzheimer's.

Recent studies in rodents have found the bacteria do infect regions of the brain affected by Alzheimer's, that gum infections can worsen symptoms in mice genetically engineered to get Alzheimer's, and that gum infections can seemingly lead to brain inflammation and amyloid plaques in previously healthy mice. Brains with more gingipains had higher quantities of the Alzheimer's-linked proteins tau and ubiquitin.

Interestingly, the brains of 50 control bodies, who were elderly but did not suffer from Alzheimer's, contained low levels of gingipains. That early appearance is important, Lynch says, because "you would expect it to be there before the onset" of symptoms.

However, he said the study was limited because the team has not yet determined if different strains of P. gingivalis are more virulent than others in causing brain infection.

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The experiment in mice showed "small increases in the levels of one of the Alzheimer's associated proteins with Pg infection that were prevented with the experimental drug", commented Tara Spires-Jones, deputy director of the Centre for Discovery Brain Sciences at the University of Edinburgh. In a lab dish, the gingipains-whose job is to chop up proteins-damaged tau, a regularly occurring brain protein that forms tangles in people with Alzheimer's.

There was also caution about the fact the drug tests had been in mice. Targeting gingipains likely works by cutting off nutrients and other molecules that the enzyme supplies to the bacteria, Dominy says.

In October 2018, Cortexyme announced encouraging results from its Phase 1b clinical trial of COR388 at the 11th Clinical Trials in Alzheimer's Disease Conference. A larger study is slated to start this year.

Spires-Jones added that Alzheimer's disease patients also have disruption of their blood-brain barriers, "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". "These are odd ideas, but they seem to be getting some traction".

The bacteria was found in three brain tissue DNA samples. Too much of this protective response to pathogens could trigger the buildup of the disease's signature amyloid plaques, they suggest.

P. gingivalis can destroy gums and cause tooth loss. But he's skeptical that the bacteria or its toxin directly cause Alzheimer's.

It's possible that news of the possible link will lead to people spending more time on their dental health than they now do, though: One study found less than one third of Americans floss daily.

Understanding that process has revealed potential drug targets, she said, since repressive histone modification is controlled or catalyzed by enzymes.

One way to do that is to attend a Dementia Friendly training event like the one I will be hosting in conjunction with the Alzheimer's Society at the Age UK Roundhouse in Ashington on Friday, February 8, at 11.30am.

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