By Maryam Sarah Ahmed
Alzheimer’s disease results in loss of memory and thinking skills, communication problems, and behavioural issues. These symptoms occur because of the damage and loss of brain cells, called neurons, but the exact cause for this neurodegenerative disease is still unknown. Recent studies, however, suggest that a certain kind of mouth bacteria – Porphyromonas gingivalis – may actually be the cause of Alzheimer’s disease. P. gingivalis is a type of bacteria that can cause gum disease. They can spread from the mouth to the bloodstream, and from there these bacteria can reach other tissues. A 2019 study showed that P. gingivalis was found in the cerebral cortex of the brains of Alzheimer’s patients. The cerebral cortex is the part of the brain which is associated with thinking skills and language, and is one of the parts that gets damaged as the disease progresses. Although P. gingivalis was also found in healthy brains, the levels of this bacteria were far higher in the brains of Alzheimer’s patients. This suggests that P. gingivalis may play a role in the onset of Alzheimer’s. Exactly how these bacteria may cause Alzheimer’s is still uncertain, but there are many possibilities. One way they might cause damage is by triggering the harmful buildup of proteins. Most Alzheimer’s patients have abnormal structures called amyloid plaques and neurofibrillary tangles (also called tau tangles) in their brains. Amyloid is a type of protein which, in this disease, is found in unusually high levels in the brain and obstructs neuron function by forming large clumps between the brain cells. Tau is another kind of protein that groups together, forming tangles inside neurons and thus blocks communication between different neurons. P. gingivalis produces enzymes (special proteins which are involved in chemical reactions in the body) called gingipains, which can enable the formation of amyloid plaques and tau tangles. These bacteria can even enter neurons and produce these gingipain enzymes within the neurons themselves. Another way P. gingivalis may result in Alzheimer’s is by causing brain inflammation, which can damage and kill neurons. In addition, these gingipains are also involved in breaking down iron-containing proteins to release iron. Iron accumulation in the brain has been linked with Alzheimer’s, as excessive amounts of iron stimulate toxicity in amyloid proteins and also promote the formation of plaques and tangles. Therefore, P. gingivalis in the brain may result in this accumulation of iron and thus cause Alzheimer’s. Although it has not yet been confirmed that P. gingivalis infection triggers Alzheimer’s, these findings strongly suggest causation and may help in discovering new treatments for the disease. At the very least it gives an extra incentive to maintain good oral hygiene.
References
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 advances, 5(1). doi: 10.1126/sciadv.aau3333
Guo, Y., Nguyen, K. A., & Potempa, J. (2010). Dichotomy of gingipains action as virulence factors: from cleaving substrates with the precision of a surgeon's knife to a meat chopper-like brutal degradation of proteins. Periodontology 2000, 54(1), 15-44. doi:10.1111/j.1600-0757.2010.00377.x
Kanagasingam, S., Chukkapalli, S. S., & Welbury, R. &. (2020). Porphyromonas gingivalis is a Strong Risk Factor for Alzheimer's Disease. Journal of Alzheimer's disease reports, 4(1), 501-511. doi:10.3233/ADR-200250
Liu, B. M., Serpell, L. C., Hider, R., Marciniak, S. J., Lomas, D. A., & Crowther, D. C. (2011). Iron promotes the toxicity of amyloid beta peptide by impeding its ordered aggregation. The Journal of biological chemistry, 286(6), 4248-4256. doi:10.1074/jbc.M110.158980
Liu, J. L., Fan, Y. G., Yang, Z. S., Wang, Z. Y., & Guo, C. (2018). Iron and Alzheimer's Disease: From Pathogenesis to Therapeutic Implications. Frontiers in neuroscience, 12, 632. doi:10.3389/fnins.2018.00632
Mackenzie, D. (2019, January 23). We may finally know what causes Alzheimer’s – and how to stop it. Retrieved from NewScientist: https://www.newscientist.com/article/2191814-we-may-finally-know-what-causes-alzheimers-and-how-to-stop-it/
U.S. Department of Health and Human Services, National Institute of Health, National Institute of Aging. (2017, May 16). What Are the Signs of Alzheimer's Disease? Retrieved from https://www.nia.nih.gov/health/what-are-signs-alzheimers-disease
U.S. Department of Health and Human Services, National Institute of Health, National Institute of Aging. (2017, May 16). What Happens to the Brain in Alzheimer's Disease? Retrieved from https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease