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Eukaryon

Porphyromonas gingivalis as a possible cause of Alzheimer’s Disease

Andrew Forrest
Lake Forest College
Lake Forest, Illinois 60045

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by the worsening of memory and thinking abilities (1). The loss of these functions often slowly leads to an inability of those suffering from the disease to complete most tasks without help. 

Globally, AD is the sixth leading cause of death, and it is the most common cause of dementia (1). Despite its prevalence and devastating effects, research towards finding more effective treatments for AD has not been very successful. According to one study, 99 percent of new drugs that have been developed to treat AD have failed (Cummings et al. 2018). Many drugs that are successful are only slightly able to reduce symptoms and do not greatly slow the progression of the disease. 

Some scientists believe that new drugs likely have not provided effective  treatments because they do not prevent the mechanisms thatcauseing the disease. It has been known for some time that the accumulation of amyloid proteins in the brain is related in some way to the development and progression of AD. It was thought that AD was caused by defective control of amyloid protein (4). Amyloid protein aggregations are found in the brains of many patients with AD, and they are often some of the first pathological signs of AD. As a result, previous studies have focused on finding ways to prevent amyloid proteins from aggregating.

In the past few years, some research has focused on trying to find other possible causes of AD. In 2016, amyloid was discovered to help to defend against bacterial infection. This has led to new studies being conducted that focus on bacteria as a cause of AD, and amyloid aggregation as a symptom (4). 

A study completed by Dominy et al. (2019) from the pharmaceutical firm Cortexyme found that the bacterium Porphyromonas gingivalis may cause AD. P. gingivalis is known to cause gum disease; however, it has recently been discovered to also be found in animals with Alzheimer’s-like diseases. AD is a disease that occurs in humans, but  researchers in this study demonstrated that AD like diseases could occur in mice as a result of bacterial infection. By giving mice P. gingivalis gum disease, the researchers found that the bacteria could spread to the brain and cause an  infection that led to amyloid plaque formation surrounding the bacteria and neuronal death (Dominy et al.)

The study also verified that P. gingivalis has been found in brains of people suffering from AD. Gingipains that are produced by P. gingivalis were found in ~96% of brain tissue samples taken from the hippocampus of 54 patients with AD (Dominy et al.). Figure 1 presents data collected from human AD patients that further connects initial P. gingivalis gum infection with the spread of the bacteria to the brain and to the development of AD. 

Figure 1. A shows P. gingivalis found in cerebrospinal fluid (CSF) and B shows P. gingivalis found in saliva of AD patients. Many patients who have AD present both gum and brain P. gingivalis infection (Dominy et al. 2019).

Figure 1. A shows P. gingivalis found in cerebrospinal fluid (CSF) and B shows P. gingivalis found in saliva of AD patients. Many patients who have AD present both gum and brain P. gingivalis infection (Dominy et al. 2019).

The research collected by Dominy et al. presents new information about a possible cause of AD that has not been considered before. Their data supports that P. gingivalis infection is correlated with AD occurrence. The researchers that conducted this study are hopeful that this information could lead to the development of new drugs that could improve treatment of AD.

However, many other scientists are uncertain whether P. gingivalis is a significant cause of AD, and they believe that there are likely other factors that influence the development of the disease that should be considered. More studies must be completed to determine how P. gingivalis may cause AD, and how new drugs could be used to prevent AD if this is the case. Neurodegeneration caused by P. gingivalis has been prevented in early treatments involving gingipain inhibitors (Dominy et al.), and further studies of this type of treatment will allow  scientists to verify whether or not it is  effective.

The effectiveness of new treatments directed towards preventing amyloid aggregation can also be studied to look for viable treatment options for this pathology. A biotechnology company, Biogen, recently developed a drug that has been effective in slowing the progression of AD in trials by reducing amyloid aggregation. Whether or not this drug is effective for treating AD will likely be influential in determining how AD will be treated in the future.

 

References

Alzheimer’s Disease Fact Sheet. (n.d.). Retrieved October 22, 2019, from https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet.

Dominy, S. S., Lynch, C., Ermini, F., Benedyk, M., Marczyk, A., Konradi, A., … Potempa, J. (2019). Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science Advances5(1). doi: 10.1126/sciadv.aau3333

JeffreyCummingsa. (2018, June 13). The price of progress: Funding and financing Alzheimer’s disease drug development. Retrieved October 22, 2019, from https://www.sciencedirect.com/science/article/pii/S235287371830026X.

MacKenzie, D. (2019, January 30). We may finally know what causes Alzheimer’s – and how to stop it. Retrieved October 22, 2019, from https://www.newscientist.com/article/2191814-we-may-finally-know-what-causes-alzheimers-and-how-to-stop-it/.

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