Gum Disease Bacteria More Common in the Brains of Alzheimer's Patients

Researchers here note that the bacteria associated with gum disease are found more frequently in the brains of Alzheimer's disease patients. While looking over this research, it is worth bearing in mind that a recent large study found only a 6% increased risk of dementia in patients with periodontitis. So rather than thinking that there is a very large contribution to the disease process here, we might consider an alternative model: that people with Alzheimer's disease may be more likely to have a leaky blood-brain barrier, allowing greater traffic of normally forbidden molecules, cells, and pathogens into the brain. Vascular dysfunction is common in Alzheimer's patients, many of whom also exhibit vascular dementia in addition to the signs and symptoms of Alzheimer's disease. Thus the infiltration of bacteria into the brain may be a consequence of underlying damage rather than a cause of it, and this bacterial infiltration, while being clearly associated with disease-related mechanisms, may cause only modest additional harm over and above the more direct consequences of that damage.

The bacterium, Porphyromonas gingivalis, is the bad actor involved in periodontitis, the most serious form of gum disease. While previous researchers have noted the presence of P. gingivalis in brain samples from Alzheimer's patients, new results offer the strongest evidence to date that the bacterium may actually contribute to the development of Alzheimer's disease. The researchers compared brain samples from deceased people with and without Alzheimer's disease who were roughly the same age when they died. They found P. gingivalis was more common in samples from Alzheimer's patients, evidenced by the bacterium's DNA fingerprint and the presence of its key toxins, known as gingipains.

In studies using mice, they showed P. gingivalis can move from the mouth to the brain and that this migration can be blocked by chemicals that interact with gingipains. An experimental drug from Cortexyme that blocks gingipains, known as COR388, is currently in phase 1 clinical trials for Alzheimer's disease. Researchers are working on other compounds that block enzymes important to P. gingivalis and other gum bacteria in hopes of interrupting their role in advancing Alzheimer's and other diseases.

The researchers also report evidence on the bacterium's role in the autoimmune disease rheumatoid arthritis, as well as aspiration pneumonia, a lung infection caused by inhaling food or saliva. "P. gingivalis's main toxins, the enzymes the bacterium need to exert its devilish tasks, are good targets for potential new medical interventions to counteract a variety of diseases. The beauty of such approaches in comparison to antibiotics is that such interventions are aimed only at key pathogens, leaving alone good, commensal bacteria, which we need."

Link: https://www.eurekalert.org/pub_releases/2019-04/eb-gbi032819.php

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