ALZHEİMER HASTALIĞI İLE PERİODONTAL HASTALIKLAR ARASINDA BİR İLİŞKİ OLABİLİR Mİ?

Year 2022, Volume: 9 Issue: 2, 675 - 684, 24.08.2022

Beyza Olukpınar Genç , Tanju Kadir

https://doi.org/10.15311/selcukdentj.972749

Cited By: 1

Abstract

Alzheimer hastalığı (AH), antimikrobiyal peptit olarak bilinen β-amiloid birikimi ve anormal şekilde fosforile tau proteinlerinden oluşan nörofibriler yumakların varlığı ile karakterize nöroinflamatuar ve nörodejeneratif bir hastalık olarak tanımlanır. Periodontal hastalığın patogenezinde rol oynayan Porphyromonas gingivalis (P. gingivalis) AH ile ilişkili önemli bakteriyel patojenden biri olarak kabul edilmiştir. Ağız boşluğunda bulunan bu bakteriye ait metabolik yan ürünlerinin ağız boşluğunun ötesinde bağışıklık sistemini aktive edebildiği böylece sistemik koşulların gelişimini teşvik edebildiği gözlenmiştir. Artan sayıda yapılan çalışmalar P. gingivalis'in beyin kolonizasyonunun inflamatuar ve dejeneratif durumu birbirine bağlayabileceğini bildirmiştir. AH'li kişilerin beyinlerinden alınan otopsi örneklerinde ve beyin omurilik sıvılarında P. gingivalis infiltrasyonunun varlığı tespit edilmiştir. P. gingivalis tarafından üretilen proteaz sınıfı olan gingipainlerin AH'li bireylerin beyinlerinden alınan örneklerde nöronlar, tau yumakları ve β-amiloid ile ilişkili olduğu bulunmuştur. Yerleşik beyin enfeksiyonları olan farelere oral yoldan verilen gingipain inhibitörlerinin beyindeki P. gingivalis DNA bolluğunu ve bakteri enfeksiyonunun nörotoksik etkilerini azalttığı bildirilmiştir. Dolayısıyla gingipain inhibisyonu hem periodontitis hem de AH'nın tedavisine potansiyel bir yaklaşım sağlayabildiği düşünülmüştür. Bu derlemenin amacı, periodontal hastalık ile Alzheimer hastalığı ve demans arasında nedensel bir ilişki olasılığını değerlendirmek ve literatürlerdeki daha fazla araştırma gerektiren temel boşlukları belirlemek olmuştur.

Keywords

Alzheimer hastalığı, Porphyromonas gingivalis, Periodontal hastalıklar, Gingipain

References

• 1. Newman MG, H.Tahei H, Klokkevold PR, Carranza FA. Newman and Carranza’s Clinical Periodontology, 13th Edition. 13th ed. (Carranza FA, Satheesh Elangovan, Marcelo Freire, Søren Jepsen, Perry R. Klokkevold, Newman MG, eds.).; 2019.
• 2. Caufield PW, Dasanayake AP, Li Y, Pan Y, Hsu J, Hardin JM. Natural history of Streptococcus sanguinis in the oral cavity of infants: Evidence for a discrete window of infectivity. Infect Immun. 2000. doi:10.1128/IAI.68.7.4018-4023.2000
• 3. Stingu CS, Eschrich K, Rodloff AC, Schaumann R, Jentsch H. Periodontitis is associated with a loss of colonization by Streptococcus sanguinis. J Med Microbiol. 2008. doi:10.1099/jmm.0.47649-0
• 4. Darveau RP, Hajishengallis G, Curtis MA. Porphyromonas gingivalis as a potential community activist for disease. J Dent Res. 2012. doi:10.1177/0022034512453589
• 5. Abusleme L, Dupuy AK, Dutzan N, et al. The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation. ISME J. 2013. doi:10.1038/ismej.2012.174
• 6. CDC researchers find close to half of American adults have periodontitis. J Can Dent Assoc. 2012.
• 7. Whitmore SE, Lamont RJ. Oral Bacteria and Cancer. PLoS Pathog. 2014. doi:10.1371/journal.ppat.1003933
• 8. Bui FQ, Almeida-da-Silva CLC, Huynh B, et al. Association between periodontal pathogens and systemic disease. Biomed J. 2019;42:27-35. doi:10.1016/j.bj.2018.12.001
• 9. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL. Microbial complexes in subgingival plaque. J Clin Periodontol. 1998;25(2):134-144. doi:10.1111/j.1600-051X.1998.tb02419.x
• 10. Gaur S, Agnihotri R. Alzheimer’s disease and chronic periodontitis: Is there an association? Geriatr Gerontol Int. 2015. doi:10.1111/ggi.12425
• 11. Bondi MW, Edmonds EC, Salmon DP. Alzheimer’s disease: Past, present, and future. J Int Neuropsychol Soc. 2017. doi:10.1017/S135561771700100X
• 12. Wu YT, Beiser AS, Breteler MMB, et al. The changing prevalence and incidence of dementia over time-current evidence. Nat Rev Neurol. 2017. doi:10.1038/nrneurol.2017.63
• 13. Kamer AR, Craig RG, Niederman R, Fortea J, de Leon MJ. Periodontal disease as a possible cause for Alzheimer’s disease. Periodontol 2000. 2020. doi:10.1111/prd.12327
• 14. Kamer AR, Craig RG, Dasanayake AP, Brys M, Glodzik-Sobanska L, de Leon MJ. Inflammation and Alzheimer’s disease: Possible role of periodontal diseases. Alzheimer’s Dement. 2008. doi:10.1016/j.jalz.2007.08.004
• 15. Daly B, Thompsell A, Sharpling J, et al. Evidence summary: The relationship between oral health and dementia. Br Dent J. 2018. doi:10.1038/sj.bdj.2017.992
• 16. Gusman DJR, Mello-Neto JM, Alves BES, et al. Periodontal disease severity in subjects with dementia: A systematic review and meta-analysis. Arch Gerontol Geriatr. 2018. doi:10.1016/j.archger.2018.02.016
• 17. Maldonado A, Laugisch O, Bürgin W, Sculean A, Eick S. Clinical periodontal variables in patients with and without dementia—a systematic review and meta-analysis. Clin Oral Investig. 2018. doi:10.1007/s00784-018-2523-x
• 18. Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991. doi:10.1007/BF00308809
• 19. Goto T, Kuramoto E, Dhar A, et al. Neurodegeneration of Trigeminal Mesencephalic Neurons by the Tooth Loss Triggers the Progression of Alzheimer’s Disease in 3×Tg-AD Model Mice. J Alzheimer’s Dis. 2020. doi:10.3233/JAD-200257
• 20. Kanagasingam S, Chukkapalli SS, Welbury R, Singhrao SK. Porphyromonas gingivalis is a Strong Risk Factor for Alzheimer’s Disease. J Alzheimer’s Dis Reports. 2020. doi:10.3233/adr-200250
• 21. Hajishengallis G, Darveau RP, Curtis MA. The keystone-pathogen hypothesis. Nat Rev Microbiol. 2012. doi:10.1038/nrmicro2873
• 22. Riviere G, Riviere KH, Smith KS. Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer’s disease. Oral Microbiol Immunol. 2002. doi:10.1046/j.0902-0055.2001.00100.x
• 23. Dominy SS, Lynch C, Ermini F, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019. doi:10.1126/sciadv.aau3333
• 24. Chen J, Ren C-J, Wu L, et al. Tooth Loss Is Associated With Increased Risk of Dementia and With a Dose-Response Relationship. Front Aging Neurosci. 2018. doi:10.3389/fnagi.2018.00415
• 25. Akiyama H, Barger S, Barnum S, et al. Inflammation and Alzheimer’s disease. Neurobiol Aging. 2000. doi:10.1016/S0197-4580(00)00124-X
• 26. Singhrao SK, Harding A. Is Alzheimer’s disease a polymicrobial host microbiome dysbiosis? Expert Rev Anti Infect Ther. 2020. doi:10.1080/14787210.2020.1729741
• 27. Olsen I, Singhrao SK. Interaction between genetic factors, Porphyromonas gingivalis and microglia to promote Alzheimer’s disease. J Oral Microbiol. 2020. doi:10.1080/20002297.2020.1820834
• 28. Yip AG, McKee AC, Green RC, et al. APOE, vascular pathology, and the AD brain. Neurology. 2005. doi:10.1212/01.wnl.0000168863.49053.4d
• 29. Jin YP, Østbye T, Feightner JW, Di Legge S, Hachinski V. Joint effect of stroke and APOE 4 on dementia risk: The Canadian Study of Health and Aging. Neurology. 2008. doi:10.1212/01.wnl.0000284609.77385.03
• 30. Xu W, Tan L, Wang HF, et al. Meta-analysis of modifiable risk factors for Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2015. doi:10.1136/jnnp-2015-310548
• 31. Kulashekar M, Stom SM, Peuler JD. Resveratrol’s potential in the adjunctive management of cardiovascular disease, obesity, diabetes, Alzheimer disease, and cancer. J Am Osteopath Assoc. 2018. doi:10.7556/jaoa.2018.133
• 32. Li L, Cavuoto M, Biddiscombe K, Pike KE, Ravona-Springer R. Diabetes Mellitus Increases Risk of Incident Dementia in APOE ϵ4 Carriers: A Meta-Analysis. J Alzheimer’s Dis. 2020. doi:10.3233/JAD-191068
• 33. Montagne A, Barnes SR, Sweeney MD, et al. Blood-Brain barrier breakdown in the aging human hippocampus. Neuron. 2015. doi:10.1016/j.neuron.2014.12.032
• 34. Goodall EF, Wang C, Simpson JE, et al. Age-associated changes in the blood-brain barrier: comparative studies in human and mouse. Neuropathol Appl Neurobiol. 2018. doi:10.1111/nan.12408
• 35. Montagne A, Nation DA, Pa J, Sweeney MD, Toga AW, Zlokovic B V. Brain imaging of neurovascular dysfunction in Alzheimer’s disease. Acta Neuropathol. 2016. doi:10.1007/s00401-016-1570-0
• 36. Halliday MR, Rege S V., Ma Q, et al. Accelerated pericyte degeneration and blood-brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer’s disease. J Cereb Blood Flow Metab. 2016. doi:10.1038/jcbfm.2015.44
• 37. Singhrao SK, Chukkapalli S, Poole S, Velsko I, Crean SJ, Kesavalu L. Chronic porphyromonas gingivalis infection accelerates the occurrence of age-related granules in ApoE-/- mice brains. J Oral Microbiol. 2017. doi:10.1080/20002297.2016.1270602
• 38. Rokad F, Moseley R, Hardy RS, et al. Cerebral Oxidative Stress and Microvasculature Defects in TNF-α Expressing Transgenic and Porphyromonas gingivalis -Infected ApoE-/- Mice. J Alzheimer’s Dis. 2017. doi:10.3233/JAD-170304
• 39. Sheets SM, Potempa J, Travis J, Casiano CA, Fletcher HM. Gingipains from Porphyromonas gingivalis W83 induce cell adhesion molecule cleavage and apoptosis in endothelial cells. Infect Immun. 2005. doi:10.1128/IAI.73.3.1543-1552.2005
• 40. Lv S, Song HL, Zhou Y, et al. Tumour necrosis factor-α affects blood-brain barrier permeability and tight junction-associated occludin in acute liver failure. Liver Int. 2010. doi:10.1111/j.1478-3231.2010.02211.x
• 41. Vernal R, León R, Silva A, Van Winkelhoff AJ, Garcia-Sanz JA, Sanz M. Differential cytokine expression by human dendritic cells in response to different Porphyromonas gingivalis capsular serotypes. J Clin Periodontol. 2009. doi:10.1111/j.1600-051X.2009.01462.x
• 42. Olsen I, Singhrao SK. Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signalling. J Oral Microbiol. 2018. doi:10.1080/20002297.2018.1440128
• 43. Zenobia C, Hasturk H, Nguyen D, Van Dyke TE, Kantarci A, Darveaua RP. Porphyromonas gingivalis lipid a phosphatase activity is critical for colonization and increasing the commensal load in the rabbit ligature model. Infect Immun. 2014. doi:10.1128/IAI.01136-13
• 44. Farhad SZ, Amini S, Khalilian A, et al. The effect of chronic periodontitis on serum levels of tumor necrosis factor-alpha in Alzheimer disease. Dent Res J (Isfahan). 2014.
• 45. Stein PS, Desrosiers M, Donegan SJ, Yepes JF, Kryscio RJ. Tooth loss, dementia and neuropathology in the Nun Study. J Am Dent Assoc. 2007. doi:10.14219/jada.archive.2007.0046
• 46. Rubio-Perez JM, Morillas-Ruiz JM. A review: Inflammatory process in Alzheimer’s disease, role of cytokines. Sci World J. 2012. doi:10.1100/2012/756357
• 47. Kamer AR, Craig RG, Pirraglia E, et al. TNF-α and antibodies to periodontal bacteria discriminate between Alzheimer’s disease patients and normal subjects. J Neuroimmunol. 2009. doi:10.1016/j.jneuroim.2009.08.013
• 48. Poole S, Singhrao SK, Kesavalu L, Curtis MA, Crean SJ. Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer’s disease brain tissue. J Alzheimer’s Dis. 2013. doi:10.3233/JAD-121918
• 49. Ellen RP, Galimanas VB. Spirochetes at the forefront of periodontal infections. Periodontol 2000. 2005. doi:10.1111/j.1600-0757.2005.00108.x
• 50. Roulis E, Bachmann NL, Myers GSA, et al. Comparative genomic analysis of human Chlamydia pneumoniae isolates from respiratory, brain and cardiac tissues. Genomics. 2015. doi:10.1016/j.ygeno.2015.09.008
• 51. Hammond CJ, Hallock LR, Howanski RJ, Appelt DM, Little CS, Balin BJ. Immunohistological detection of Chlamydia pneumoniae in the Alzheimer’s disease brain. BMC Neurosci. 2010. doi:10.1186/1471-2202-11-121
• 52. Poole S, Singhrao SK, Chukkapalli S, et al. Active invasion of Porphyromonas gingivalis and infection-induced complement activation in ApoE-/- mice brains. J Alzheimer’s Dis. 2014. doi:10.3233/JAD-140315
• 53. Sparks Stein P, Steffen MJ, Smith C, et al. Serum antibodies to periodontal pathogens are a risk factor for Alzheimer’s disease. Alzheimer’s Dement. 2012. doi:10.1016/j.jalz.2011.04.006
• 54. Smalley JW, Birss AJ, Kay HM, McKee AS, Marsh. PD. The distribution of trypsin‐like enzyme activity in cultures of a virulent and an a virulent strain of Bacteroides gingivalis W50. Oral Microbiol Immunol. 1989. doi:10.1111/j.1399-302X.1989.tb00249.x
• 55. Potempa J, Pike R, Travis J. The multiple forms of trypsin-like activity present in various strains of Porphyromonas gingivalis are due to the presence of either Arg-gingipain or Lys-gingipain. Infect Immun. 1995. doi:10.1128/iai.63.4.1176-1182.1995
• 56. Imamura T. The Role of Gingipains in the Pathogenesis of Periodontal Disease. J Periodontol. 2003. doi:10.1902/jop.2003.74.1.111
• 57. Tsutsui H, Kinouchi T, Wakano Y, Ohnishi Y. Purification and characterization of a protease from Bacteroides gingivalis 381. Infect Immun. 1987. doi:10.1128/iai.55.2.420-427.1987
• 58. Cabrales Fontela Y, Kadavath H, Biernat J, Riedel D, Mandelkow E, Zweckstetter M. Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau. Nat Commun. 2017. doi:10.1038/s41467-017-02230-8
• 59. Abe N, Kadowaki T, Okamoto K, Nakayama K, Ohishi M, Yamamoto K. Biochemical and functional properties of lysine-specific cysteine proteinase (Lys-Gingipain) as a virulence factor of Porphyromonas gingivalis in periodontal disease. J Biochem. 1998. doi:10.1093/oxfordjournals.jbchem.a021937
• 60. Ryder MI. Porphyromonas gingivalis and Alzheimer disease: Recent findings and potential therapies. J Periodontol. 2020. doi:10.1002/JPER.20-0104
• 61. Haditsch U, Roth T, Rodriguez L, et al. Alzheimer’s Disease-Like Neurodegeneration in Porphyromonas gingivalis Infected Neurons with Persistent Expression of Active Gingipains. J Alzheimer’s Dis. 2020. doi:10.3233/JAD-200393
• 62. Goedert M, Klug A, Crowther RA. Tau protein, the paired helical filament and Alzheimer’s disease. J Alzheimer’s Dis. 2006. doi:10.3233/jad-2006-9s323
• 63. Siddiqui H, Eribe ER, Singhrao SK, Olsen I. High Throughput Sequencing Detect Gingivitis And Periodontal Oral Bacteria In Alzheimer’s Disease Autopsy Brains. Neuro Res. 2019. doi:10.35702/nrj.10003
• 64. Balin BJ, Gérard HC, Arking EJ, et al. Identification and localization of Chlamydia pneumoniae in the Alzheimer’s brain. Med Microbiol Immunol. 1998. doi:10.1007/s004300050071
• 65. Itzhaki RF, Wozniak MA. Herpes simplex virus type 1, apolipoprotein E, and cholesterol: A dangerous liaison in Alzheimer’s disease and other disorders. Prog Lipid Res. 2006. doi:10.1016/j.plipres.2005.11.003
• 66. Miklossy J. Alzheimer’s disease - a neurospirochetosis. Analysis of the evidence following Koch’s and Hill’s criteria. J Neuroinflammation. 2011. doi:10.1186/1742-2094-8-90
• 67. Grabe HJ, Schwahn C, Völzke H, et al. Tooth loss and cognitive impairment. J Clin Periodontol. 2009. doi:10.1111/j.1600-051X.2009.01426.x
• 68. Chen CK, Wu YT, Chang YC. Association between chronic periodontitis and the risk of Alzheimer’s disease: A retrospective, population-based, matched-cohort study. Alzheimer’s Res Ther. 2017. doi:10.1186/s13195-017-0282-6
• 69. Choi S, Kim K, Chang J, et al. Association of Chronic Periodontitis on Alzheimer’s Disease or Vascular Dementia. J Am Geriatr Soc. 2019. doi:10.1111/jgs.15828
• 70. Gil-Montoya JA, Barrios R, Santana S, et al. Association Between Periodontitis and Amyloid β Peptide in Elderly People With and Without Cognitive Impairment. J Periodontol. 2017. doi:10.1902/jop.2017.170071
• 71. Kamer AR, Pirraglia E, Tsui W, et al. Periodontal disease associates with higher brain amyloid load in normal elderly. Neurobiol Aging. 2015. doi:10.1016/j.neurobiolaging.2014.10.038
• 72. Mougeot JLC, Stevens CB, Paster BJ, Brennan MT, Lockhart PB, Mougeot FKB. Porphyromonas gingivalis is the most abundant species detected in coronary and femoral arteries. J Oral Microbiol. 2017. doi:10.1080/20002297.2017.1281562
• 73. Ishikawa M, Yoshida K, Okamura H, et al. Oral Porphyromonas gingivalis translocates to the liver and regulates hepatic glycogen synthesis through the Akt/GSK-3β signaling pathway. Biochim Biophys Acta - Mol Basis Dis. 2013. doi:10.1016/j.bbadis.2013.07.012
• 74. Ilievski V, Zuchowska PK, Green SJ, et al. Chronic oral application of a periodontal pathogen results in brain inflammation, neurodegeneration and amyloid beta production in wild type mice. PLoS One. 2018. doi:10.1371/journal.pone.0204941
• 75. Guo Y, Nguyen KA, Potempa J. 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. Periodontol 2000. 2010. doi:10.1111/j.1600-0757.2010.00377.x