Gum disease bug linked to Alzheimer’s (and new drug is being tested)

Credit Wikimedia Commons

Credit Wikimedia Commons

'Based on these findings, we believe that P. gingivalis is the main cause of Alzheimer's disease, and the gingipains are the main drivers of Alzheimer's pathology, ' Dominy says.

That's important, because while P. gingivalis and the disease have been linked before, it's never been known - to put it simply - whether gum disease causes Alzheimers, or whether dementia leads to poor oral care.

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.

Traditional broad-spectrum antibiotics would probably be ineffective against P. gingivalis in the brain, according to the research.

Other research has looked at whether various bacterial, viral, or fungal infections may play a role in Alzheimer's, but there is now not enough evidence to say.

In animal models, oral Pg infection led to brain colonization and increased production of amyloid beta (Aβ), a component of the amyloid plaques commonly associated with AD.

"I'm much less convinced that [it] causes Alzheimer's disease", Robert Moir, a neurobiologist at Massachusetts General Hospital in Boston who was not involved in the study, tells Science. At the time, he was treating people with HIV at the University of California, San Francisco.

A common gum disease bug plays a "central role" in the development of Alzheimer's, scientists claim.

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The bacteria assaults the brain cells with a hostile protein while also promoting the formation of plaques in brain tissue that are found in Alzheimer's patients. They also discovered the bacterium's DNA in their spinal fluid and toxic enzymes called gingipains, which are produced by the microbe, in their brains. Another physical characteristic of the Alzheimer's diseased brain is the buildup of tau proteins, which tangle inside neurons, blocking their transport system.

The scientists tested more than 50 brain tissue samples and found that 96% contained one type of gingipain enzyme and 91% another. That early appearance is important, Lynch says, because "you would expect it to be there before the onset" of symptoms.

The researchers say they have also begun "new drug application-enabling studies" with the gingipain-inhibiting substance tested here.

Risk Factors involved with the disease and that age is the greatest known risk factor for Alzheimer's, include an individuals risk for developing Alzheimer's increases after the age of 65, having a parent or sibling with the disease increases an individuals risk and 5.7 million people are now living with Alzheimer's. A larger study is slated to start this year. "But what this paper suggests is really an association and not causation and that should be very clearly emphasized when we're talking about studies like this".

To study whether levels of the protein in blood also reflect neurological damage, researchers turned to a group of families with rare genetic variants that cause Alzheimer's at a young age-typically in a person's 50s, 40s, or even 30s.

David Reynolds, chief scientific officer at Alzheimer's Research UK, says that the idea of gum disease having a link to Alzheimer's disease has been circulating for a number of years, but that this work is "a step forward". "These are unusual ideas, but they seem to be getting some traction".

"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. In follow-up studies in mice, the researchers also found that sleeplessness speeds up the spread of toxic clumps of tau in the brain, a precursor to brain damage and dementia.

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