April 20, 2019

Gum disease bug could play key role in Alzheimer's, research suggests

26 January 2019, 05:16 | Silvia Roy

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Scientists at the company Cortexyme, working with academics from around the world, say the findings of their study could lead to new treatment options for Alzheimer's disease sufferers that work by targeting the bacterium Porphyromonas gingivalis, and they have developed a candidate drug that is now undergoing clinical trials.

The families form the study population of the Dominantly Inherited Alzheimer's Network (DIAN), an global consortium that is investigating the roots of Alzheimer's disease.

Working with labs in Europe, the United States, New Zealand, and Australia, the Cortexyme team confirmed earlier reports that P. gingivalis can be found in the brains of deceased people with Alzheimer's, and they detected the microbe's DNA in living patients' spinal fluid.

"Our identification of gingipain antigens in the brains of individuals with AD and also with AD pathology but no diagnosis of dementia argues that brain infection with P. gingivalis is not a result of poor dental care following the onset of dementia or a effect of late-stage disease, but is an early event that can explain the pathology found in middle-aged individuals before cognitive decline", the authors write in their paper.

And when they watched P. gingivalis infections play out in mice, it triggered neurodegeneration in the hippocampus, a brain structure central to memory.

Casey Lynch of Cortexyme was quoted as saying some brain samples with Alzheimer's showed the presence of the bacteria and the two proteins but at lower concentrations.

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"NfL levels rise whenever the brain is damaged, and as Alzheimer's disease affects 30% of people over the age of 80, we hope that NfL will become part of a GP's standard battery, like annual cholesterol testing". 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.

"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".

Further, a compound formulated by the company called COR388, which is already going through clinical trials with Alzheimer's patients, showed in experiments with mice that it could reduce bacterial load of an established P. gingivalis brain infection, while also reducing amyloid-beta production and neuroinflammation.

According to Potempa, although infectious agents have been implicated in the development and progression of Alzheimer's disease, the evidence of causation hasn't been convincing.

The team also tested drugs in mice aimed at clearing the harmful bacteria and blocking its toxic enzymes. 'A couple of years ago it was suggested [amyloid] accumulation might actually be part of the brain's innate immune system for dealing with bacteria, ' he says.

They found P. gingivalis DNA in 7 out of 10 cerebrospinal fluid samples of people with Alzheimer's disease and all 10 matched saliva samples.

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Still, Edelmayer says with so much still unknown about the disease, studies like this are important for gaining a better understanding of Alzheimer's.

The team even managed to find a way to kill P. gingivalis in the brains of mice. In laboratory experiments, antibiotics did not prevent cell death induced by P. gingivalis. "The Science Advances publication sheds light on an unexpected driver of Alzheimer's pathology - the bacterium commonly associated with chronic periodontal disease - and details the promising therapeutic approach Cortexyme is taking to address it with COR388".

P. gingivalis can destroy gums and cause tooth loss.

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. The upcoming clinical trial will be a crucial test to see if this can be a potential treatment for Alzheimer's".

"Despite the involvement of a virus, the [Alzheimer's] disease is apparently not contagious", she told Newsweek.

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