Porphyromonas gingivalis as a link between periodontitis and Alzheimer's disease. Narrative literature review
DOI:
https://doi.org/10.33448/rsd-v12i5.41692Keywords:
Alzheimer's disease; Periodontal disease; Periodontitis; Porphyromonas gingivalis.Abstract
Alzheimer's disease (AD) is one of the most common neurodegenerative disorders in the world and has been listed as a global public health priority by the WHO. There is currently no effective treatment for the disease and its cause is still unknown. In recent years, attempts have been made to explain the etiological mechanisms of AD, one proposed hypothesis is the spread of oral microorganisms such as Porphyromonas gingivalis (Pg) to brain tissue in patients with periodontitis. However, this possible causal relationship remains unclear. Objective: to present the role of Pg as a link between periodontitis and Alzheimer's disease based on a literature review of publications from the last 5 years. Materials and methods: search of publications in the following databases: PubMed, SpringerLink, Scientific Direct, Scielo. Results: 19 scientific articles were included of which animal and molecular studies determine that, Pg infection increased the production of inflammatory mediators, thus causing an increase in the production of Aβ (beta amyloid) and subsequently, neurodegeneration compatible with AD; however, no clear relationship has been established in human studies. Conclusion: the effect of Pg on the development of neuroinflammation has been demonstrated; however, further large-scale studies and longitudinal follow-up in humans are needed to better establish the relationship between periodontitis and AD.
References
Abe, N., Baba, A., Takii, R., Nakayama, K., Kamaguchi, A., Shibata, Y., Abiko, Y., Okamoto, K., Kadowaki, T., & Yamamoto, K. (2004). Roles of Arg- and Lys-gingipains in coaggregation of Porphyromonas gingivalis: Identification of its responsible molecules in translation products of rgpA, kgp, and hagA genes. Biological Chemistry, 385(11), 1041-1047. https://doi.org/10.1515/BC.2004.135
Association, A. (2014). 2014 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia, 10(2), e47-e92. https://doi.org/10.1016/j.jalz.2014.02.001
Bao, K., Belibasakis, G. N., Thurnheer, T., Aduse-Opoku, J., Curtis, M. A., & Bostanci, N. (2014). Role of Porphyromonas gingivalis gingipains in multi-species biofilm formation. BMC Microbiology, 14, 258. https://doi.org/10.1186/s12866-014-0258-7
Braak, H., & Braak, E. (1995). Staging of Alzheimer’s disease-related neurofibrillary changes. Neurobiology of Aging, 16(3), 271-278; discussion 278-284. https://doi.org/10.1016/0197-4580(95)00021-6
Bui, F. Q., Almeida-da-Silva, C. L. C., Huynh, B., Trinh, A., Liu, J., Woodward, J., Asadi, H., & Ojcius, D. M. (2019). Association between periodontal pathogens and systemic disease. Biomedical Journal, 42(1), 27-35. https://doi.org/10.1016/j.bj.2018.12.001
Carter, C. J., France, J., Crean, S., & Singhrao, S. K. (2017). The Porphyromonas gingivalis/Host Interactome Shows Enrichment in GWASdb Genes Related to Alzheimer’s Disease, Diabetes and Cardiovascular Diseases. Frontiers in Aging Neuroscience, 9, 408. https://doi.org/10.3389/fnagi.2017.00408
Chen, C.-K., Wu, Y.-T., & Chang, Y.-C. (2017). Association between chronic periodontitis and the risk of Alzheimer’s disease: A retrospective, population-based, matched-cohort study. Alzheimer’s Research & Therapy, 9, 56. https://doi.org/10.1186/s13195-017-0282-6
Chi, L., Cheng, X., Lin, L., Yang, T., Sun, J., Feng, Y., Liang, F., Pei, Z., & Teng, W. (2021). Porphyromonas gingivalis-Induced Cognitive Impairment Is Associated With Gut Dysbiosis, Neuroinflammation, and Glymphatic Dysfunction. Frontiers in Cellular and Infection Microbiology, 11, 755925. https://doi.org/10.3389/fcimb.2021.755925
Costa, M. J. F., de Araújo, I. D. T., da Rocha Alves, L., da Silva, R. L., Dos Santos Calderon, P., Borges, B. C. D., de Aquino Martins, A. R. L., de Vasconcelos Gurgel, B. C., & Lins, R. D. A. U. (2021). Relationship of Porphyromonas gingivalis and Alzheimer’s disease: A systematic review of pre-clinical studies. Clinical Oral Investigations, 25(3), 797-806. https://doi.org/10.1007/s00784-020-03764-w
de Oliveira Araújo, R., Villoria, G. E. M., Luiz, R. R., Esteves, J. C., Leão, A. T. T., & Feres-Filho, E. J. (2021). Association between periodontitis and Alzheimer’s disease and its impact on the self-perceived oral health status: A case-control study. Clinical Oral Investigations, 25(2), 555-562. https://doi.org/10.1007/s00784-020-03489-w
Ding, Y., Ren, J., Yu, H., Yu, W., & Zhou, Y. (2018). Porphyromonas gingivalis, a periodontitis causing bacterium, induces memory impairment and age-dependent neuroinflammation in mice. Immunity & Ageing : I & A, 15, 6. https://doi.org/10.1186/s12979-017-0110-7
Dominy, S. S., Lynch, C., Ermini, F., Benedyk, M., Marczyk, A., Konradi, A., Nguyen, M., Haditsch, U., Raha, D., Griffin, C., Holsinger, L. J., Arastu-Kapur, S., Kaba, S., Lee, A., Ryder, M. I., Potempa, B., Mydel, P., Hellvard, A., Adamowicz, K., … Potempa, J. (2019). Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science Advances, 5(1). https://doi.org/10.1126/sciadv.aau3333
Eke, P. I., Dye, B. A., Wei, L., Slade, G. D., Thornton-Evans, G. O., Borgnakke, W. S., Taylor, G. W., Page, R. C., Beck, J. D., & Genco, R. J. (2015). Update on Prevalence of Periodontitis in Adults in the United States: NHANES 2009 – 2012. Journal of periodontology, 86(5), 611-622. https://doi.org/10.1902/jop.2015.140520
Fu, K.-L., Chiu, M.-J., Wara-Aswapati, N., Yang, C.-N., Chang, L.-C., Guo, Y. L., Ni, Y.-H., & Chen, Y.-W. (2022). Oral microbiome and serological analyses on association of Alzheimer’s disease and periodontitis. Oral Diseases. https://doi.org/10.1111/odi.14348
Gil Montoya, J. A., Barrios, R., Sanchez-Lara, I., Ramos, P., Carnero, C., Fornieles, F., Montes, J., Santana, S., Luna, J. de D., & Gonzalez-Moles, M. A. (2020). Systemic inflammatory impact of periodontitis on cognitive impairment. Gerodontology, 37(1), 11-18. https://doi.org/10.1111/ger.12431
Giordano-Kelhoffer, B., Lorca, C., March Llanes, J., Rábano, A., del Ser, T., Serra, A., & Gallart-Palau, X. (2022). Oral Microbiota, Its Equilibrium and Implications in the Pathophysiology of Human Diseases: A Systematic Review. Biomedicines, 10(8), 1803. https://doi.org/10.3390/biomedicines10081803
Grundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., & Binder, L. I. (1986). Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proceedings of the National Academy of Sciences of the United States of America, 83(13), 4913-4917.
Haditsch, U., Roth, T., Rodriguez, L., Hancock, S., Cecere, T., Nguyen, M., Arastu-Kapur, S., Broce, S., Raha, D., Lynch, C. C., Holsinger, L. J., Dominy, S. S., & Ermini, F. (2020). Alzheimer’s Disease-Like Neurodegeneration in Porphyromonas gingivalis Infected Neurons with Persistent Expression of Active Gingipains. Journal of Alzheimer’s Disease, 75(4), 1361. https://doi.org/10.3233/JAD-200393
Haffajee, A. D., & Socransky, S. S. (1994). Microbial etiological agents of destructive periodontal diseases. Periodontology 2000, 5, 78-111. https://doi.org/10.1111/j.1600-0757.1994.tb00020.x
Hajishengallis, G., Liang, S., Payne, M. A., Hashim, A., Jotwani, R., Eskan, M. A., McIntosh, M. L., Alsam, A., Kirkwood, K. L., Lambris, J. D., Darveau, R. P., & Curtis, M. A. (2011). A Low-Abundance Biofilm Species Orchestrates Inflammatory Periodontal Disease through the Commensal Microbiota and the Complement Pathway. Cell host & microbe, 10(5), 497-506. https://doi.org/10.1016/j.chom.2011.10.006
Hao, X., Li, Z., Li, W., Katz, J., Michalek, S. M., Barnum, S. R., Pozzo-Miller, L., Saito, T., Saido, T. C., Wang, Q., Roberson, E. D., & Zhang, P. (2022). Periodontal Infection Aggravates C1q-Mediated Microglial Activation and Synapse Pruning in Alzheimer’s Mice. Frontiers in Immunology, 13, 816640. https://doi.org/10.3389/fimmu.2022.816640
Hayashi, K., Hasegawa, Y., Takemoto, Y., Cao, C., Takeya, H., Komohara, Y., Mukasa, A., & Kim-Mitsuyama, S. (2019). Continuous intracerebroventricular injection of Porphyromonas gingivalis lipopolysaccharide induces systemic organ dysfunction in a mouse model of Alzheimer’s disease. Experimental Gerontology, 120, 1-5. https://doi.org/10.1016/j.exger.2019.02.007
Holmer, J., Eriksdotter, M., Häbel, H., Hed Myrberg, I., Jonsson, A., Pussinen, P. J., Garcia-Ptacek, S., Jansson, L., Sandborgh-Englund, G., & Buhlin, K. (2022). Periodontal conditions and incident dementia: A nationwide Swedish cohort study. Journal of Periodontology, 93(9), 1378-1386. https://doi.org/10.1002/JPER.21-0518
Ilievski, V., Zuchowska, P. K., Green, S. J., Toth, P. T., Ragozzino, M. E., Le, K., Aljewari, H. W., O’Brien-Simpson, N. M., Reynolds, E. C., & Watanabe, K. (2018). Chronic oral application of a periodontal pathogen results in brain inflammation, neurodegeneration and amyloid beta production in wild type mice. PLoS ONE, 13(10), e0204941. https://doi.org/10.1371/journal.pone.0204941
Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., & Ihara, Y. (1994). Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: Evidence that an initially deposited species is A beta 42(43). Neuron, 13(1), 45-53. https://doi.org/10.1016/0896-6273(94)90458-8
Jacques, M. (1996). Role of lipo-oligosaccharides and lipopolysaccharides in bacterial adherence. Trends in Microbiology, 4(10), 408-410. https://doi.org/10.1016/0966-842X(96)10054-8
Jungbauer, G., Stähli, A., Zhu, X., Auber Alberi, L., Sculean, A., & Eick, S. (2022). Periodontal microorganisms and Alzheimer disease – A causative relationship? Periodontology 2000, 89(1), 59-82. https://doi.org/10.1111/prd.12429
Kaliamoorthy, S., Nagarajan, M., Sethuraman, V., Jayavel, K., Lakshmanan, V., & Palla, S. (2022). Association of Alzheimer’s disease and periodontitis—A systematic review and meta-analysis of evidence from observational studies. Medicine and Pharmacy Reports, 95(2), 144-151. https://doi.org/10.15386/mpr-2278
Kamer, A. R., Pushalkar, S., Gulivindala, D., Butler, T., Li, Y., Annam, K. R. C., Glodzik, L., Ballman, K. V., Corby, P. M., Blennow, K., Zetterberg, H., Saxena, D., & Leon, M. J. de. (2021). Periodontal dysbiosis associates with reduced CSF Aβ42 in cognitively normal elderly. Alzheimer’s & Dementia : Diagnosis, Assessment & Disease Monitoring, 13(1). https://doi.org/10.1002/dad2.12172
Kassebaum, N. J., Bernabé, E., Dahiya, M., Bhandari, B., Murray, C. J. L., & Marcenes, W. (2014). Global Burden of Severe Periodontitis in 1990-2010. Journal of Dental Research, 93(11), 1045-1053. https://doi.org/10.1177/0022034514552491
Kriauciunas, A., Gleiznys, A., Gleiznys, D., & Janužis, G. (2019). The Influence of Porphyromonas Gingivalis Bacterium Causing Periodontal Disease on the Pathogenesis of Rheumatoid Arthritis: Systematic Review of Literature. Cureus, 11(5). https://doi.org/10.7759/cureus.4775
Maekawa, T., Krauss, J. L., Abe, T., Jotwani, R., Triantafilou, M., Triantafilou, K., Hashim, A., Hoch, S., Curtis, M. A., Nussbaum, G., Lambris, J. D., & Hajishengallis, G. (2014). Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis. Cell host & microbe, 15(6), 768-778. https://doi.org/10.1016/j.chom.2014.05.012
McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., Mohs, R. C., Morris, J. C., Rossor, M. N., Scheltens, P., Carrillo, M. C., Thies, B., Weintraub, S., & Phelps, C. H. (2011). The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & dementia : the journal of the Alzheimer’s Association, 7(3), 263-269. https://doi.org/10.1016/j.jalz.2011.03.005
Nazir, M., Al-Ansari, A., Al-Khalifa, K., Alhareky, M., Gaffar, B., & Almas, K. (2020). Global Prevalence of Periodontal Disease and Lack of Its Surveillance. The Scientific World Journal, 2020, 2146160. https://doi.org/10.1155/2020/2146160
Poole, S., Singhrao, S. K., Kesavalu, L., Curtis, M. A., & Crean, S. (2013). Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer’s disease brain tissue. Journal of Alzheimer’s Disease: JAD, 36(4), 665-677. https://doi.org/10.3233/JAD-121918
Qiu, C., Kivipelto, M., & von Strauss, E. (2009). Epidemiology of Alzheimer’s disease: Occurrence, determinants, and strategies toward intervention. Dialogues in Clinical Neuroscience, 11(2), 111-128.
Singhrao, S. K., Chukkapalli, S., Poole, S., Velsko, I., Crean, S. J., & Kesavalu, L. (2017). Chronic Porphyromonas gingivalis infection accelerates the occurrence of age-related granules in ApoE– / – mice brains. Journal of Oral Microbiology, 9(1), 1270602. https://doi.org/10.1080/20002297.2016.1270602
Singhrao, S. K., & Olsen, I. (2018). Are Porphyromonas gingivalis Outer Membrane Vesicles Microbullets for Sporadic Alzheimer’s Disease Manifestation? Journal of Alzheimer’s Disease Reports, 2(1), 219. https://doi.org/10.3233/ADR-180080
Tiwari, S., Atluri, V., Kaushik, A., Yndart, A., & Nair, M. (2019). Alzheimer’s disease: Pathogenesis, diagnostics, and therapeutics. International Journal of Nanomedicine, 14, 5541-5554. https://doi.org/10.2147/IJN.S200490
Wu, H., Qiu, W., Zhu, X., Li, X., Xie, Z., Carreras, I., Dedeoglu, A., Van Dyke, T., Han, Y. W., Karimbux, N., Tu, Q., Cheng, L., & Chen, J. (2022). The Periodontal Pathogen Fusobacterium nucleatum Exacerbates Alzheimer’s Pathogenesis via Specific Pathways. Frontiers in Aging Neuroscience, 14, 912709. https://doi.org/10.3389/fnagi.2022.912709
Yadav, P., Lee, Y.-H., Panday, H., Kant, S., Bajwa, N., Parashar, R., Jha, S. K., Jha, N. K., Nand, P., Lee, S.-S., & Jha, A. K. (2022). Implications of Microorganisms in Alzheimer’s Disease. Current Issues in Molecular Biology, 44(10), 4584-4615. https://doi.org/10.3390/cimb44100314
Zhang, S., Yang, F., Wang, Z., Qian, X., Ji, Y., Gong, L., Ge, S., & Yan, F. (2020). Poor oral health conditions and cognitive decline: Studies in humans and rats. PLoS ONE, 15(7), e0234659. https://doi.org/10.1371/journal.pone.0234659
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