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Periodontal Disease Link to Alzheimer’s Disease?

In the last few years a number of researchers have suggested that microbes may be triggering or somehow causing Alzheimer's disease. Various microbes have been suggested, and research is finding links with herpes viruses, fungi, other microbes, and gum disease (periodontal disease) microbes. Now another study proposes that the common bacteria Porphyromonas gingivalis - which causes chronic periodontal disease, is linked to the development of Alzheimer's disease.

Researchers have suggested that during an initial infection, the "infectious agent" (viruses, etc.) reaches the central nervous system and brain, then stays there in latent form (inactive) for years. And then when the immune system declines with age (which is a normal part of aging) - the microbes (virus, fungi, etc.) become reactivated and cause inflammation and the chain of events leading to Alzheimer's disease.

Note that in the recent study implicating P. gingivalis - the Cortexyme, Inc. company is doing the research and they, of course, are developing a product - so beware of bias. Also, the research done so far is in the earliest stages. But...it is exciting to see if further research (from them and from others) supports some sort of microbe, or several types of microbes, behind the development of Alzheimer's disease. Will we find that there is an "infectious cause" of Alzheimer's disease ("infection-induced neuroinflammation")? Because this means that there is a way to prevent or treat Alzheimer's disease - some sort of antimicrobial, antibiotic, antiviral, or antifungal. Stay tuned for further research.... From Medical Xpress:

Bacterial pathogen Porphyromonas gingivalis may contribute to Alzheimer's disease: Study

Cortexyme, Inc., a privately held, clinical-stage pharmaceutical company developing therapeutics to alter the course of Alzheimer's disease (AD) and other degenerative disorders, today announced publication of a foundational paper supporting its approach in Science Advances. In the paper, an international team of researchers led by Cortexyme co-founders Stephen Dominy, M.D. and Casey Lynch detail the role of a common bacterium, Porphyromonas gingivalis (Pg), in driving Alzheimer's disease pathology, and demonstrate the potential for small molecule inhibitors to block the pathogen. 

"Infectious agents have been implicated in the development and progression of Alzheimer's disease before, but the evidence of causation hasn't been convincing," said Stephen Dominy, M.D., Cortexyme co-founder, chief scientific officer, and lead author on the paper. "Now, for the first time, we have solid evidence connecting the intracellular, Gram-negative pathogen, Pg, and Alzheimer's pathogenesis while also demonstrating the potential for a class of small molecule therapies to change the trajectory of disease."

The Science Advances publication details how researchers identified Pg, the keystone pathogen in chronic periodontal disease, in the brains of patients with AD. In mouse models, oral Pg infection led to brain colonization and increased production of amyloid beta (Aβ), a component of the amyloid plaques commonly associated with Alzheimer's.

In addition to Pg itself, the study team also detected the organism's toxic  proteases, or gingipains, in the neurons of patients with AD. The team correlated the gingipain levels with pathology related to two markers: tau, a protein needed for normal neuronal function, and ubiquitin, a small protein tag that marks damaged proteins for degradation and is found in tau tangles and Aβ plaques. The gingipains were found to be neurotoxic in vivo and in vitro, exerting detrimental effects on tau.

"Despite significant funding and the best efforts of academic, industry, and advocacy communities, clinical progress against Alzheimer's has been frustratingly slow," said Casey Lynch, Cortexyme's co-founder, chief executive officer, and an author on the paper. "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."

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. Investigators reported the compound was safe and well tolerated in healthy older volunteers and Alzheimer's patients when given at a range of doses for up to 28 days. COR388 was detectable in the cerebral spinal fluid (CSF) along with fragmented DNA from the bacterium that COR388 targets. Additionally, while the study was not powered for significance, COR388 showed positive trends across several cognitive tests in patients suffering from AD. Cortexyme plans to initiate a large Phase 2/3 clinical trial of COR388 in mild to moderate AD in 2019.

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