Porphyromonas gingivalis, neuroinflammation and Alzheimer’s disease
DOI:
https://doi.org/10.54548/njps.v37i2.1Abstract
The oral microbiota dysbiosis, as well as lifestyle, geographical location, drug consumption, and dietary habits, are involved in the incidence and progression of dementia, Mild Cognitive Impairment (MCI), and some diseases such as obesity, diabetes, cardiovascular disease, preterm birth, rheumatoid arthritis, cancer, inflammatory bowel disease, and neurodegenerative disease e.g., Parkinson’s Disease (PD) and Alzheimer’s Disease (AD). AD is the most common cause of neurodegenerative disorder in the elderly. Also, neuroinflammation is the most common cause of AD pathogenesis. This study investigated the possible relationship between Porphyromonas gingivalis (P. gingivalis) and Alzheimer’s Disease. This review is based on research studies indexed in Scopus, Science Direct, PubMed, and Google Scholar databases. The oral microbiota comprised various microorganisms, such as fungi, archaea, and bacteria. Porphyromonas gingivalis (P. gingivalis) is one of the microorganisms, it stimulates host immune cells and releases cytokines, lysosomal enzymes, nitric oxide, and reactive oxygen species that lead to cell damage, apoptosis, and inflammation. Therefore, periodontal disease (PerioD) through systemic inflammation leads to some problems like the progression of MCI, production and aggregation of beta-amyloid (Aβ) and tau protein in the brain of the elderly population. In addition, some treatment methods could modulate the adverse effects of P. gingivalis like probiotic dietary supplements, maintaining personal hygiene, as well as gingipain inhibitors which modulate cytokines through blocked Aβ production, ApoE proteolysis, and reduced neuroinflammation. In addition, therapeutic compounds like COR388 and COR286, as gingipain inhibitors, prevent P. gingivalis colonization in the brain and have a beneficial action in some conditions like aspiration pneumonia, low birth rate, rheumatoid arthritis, PerioD and AD.
References
Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE. Defining the normal bacterial flora of the oral cavity. J Clin Microbiol. 2005 Nov;43(11):5721-32. doi: 10.1128/JCM.43.11.5721-5732.2005. PMID: 16272510; PMCID: PMC1287824.
Abbayya K, Puthanakar NY, Naduwinmani S, Chidambar YS. Association between Periodontitis and Alzheimer's Disease. N Am J Med Sci. 2015 Jun;7(6):241-6. doi: 10.4103/1947-2714.159325. PMID: 26199919; PMCID: PMC4488989.
Adams D, Koike H, Slama M, Coelho T. Hereditary transthyretin amyloidosis: A model of medical progress for a fatal disease. Nat Rev Neurol. 2019; 15, 387-404.
Allaker RP, Stephen AS. Use of probiotics and oral health. Current oral health reports. 2017 Dec;4(4):309-18.
Alvarez A, Cacabelos R, Sanpedro C, Garcia-Fantini M, Aleixandre M. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging. 2007;28(4):533–536. doi:10.1016/j.neurobiolaging.2006.02.012
Ando K, Houben S, Homa M, De Fisenne MA, Potier MC, Erneux C, et al. Alzheimer’s disease: tau pathology and dysfunction of endocytosis. Front. Mol. Neurosci.2020 ; 13:583755. doi: 10.3389/fnmol.2020.583755
Aquilano K, Vigilanza P, Filomeni G, Rotilio G, Ciriolo MR. Tau dephosphorylation and microfilaments disruption are upstream events of the anti‐proliferative effects of DADS in SH‐SY5Y cells. Journal of cellular and molecular medicine. 2010 Mar;14(3):564-77.
Arastu‐Kapur S, Nguyen M, Raha D, Ermini F, Haditsch U, Araujo J, De Lannoy IA, Ryder MI, Dominy SS, Lynch C, Holsinger LJ. Treatment of Porphyromonas gulae infection and downstream pathology in the aged dog by lysine‐gingipain inhibitor COR388. Pharmacology research & perspectives. 2020 Feb;8(1):e00562.
Bermejo-Pareja F, Antequera D, Vargas T, Molina JA, Carro E. Saliva levels of Abeta1-42 as potential biomarker of Alzheimer’s disease: A pilot study. BMC Neurol. 2010; 10, 108.
Cai Z, Hussain MD, Yan LJ. Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer's disease. International Journal of Neuroscience. 2014;124(5):307-21.
Cao J, Hou J, Ping J, Cai D. Advances in developing novel therapeutic strategies for Alzheimer’sdisease. Mol Neurodegener. 2018;13(1):64.
Chapple IL, Genco R. working group 2 of the joint EFP/AAP workshop (2013) Diabetes and periodontal diseases: consensus report of the joint EFP/AAP workshop on periodontitis and systemic diseases. J Periodontol.;84:4-Suppl.
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 research & therapy. 2017;9(1):1-7.
Chen J, Alberts I, Li X. Dysregulation of the IGF-I/PI3K/AKT/mTOR signaling pathway in autismspectrum disorders. Int. J. Dev. Neurosci. 2014, 35, 35–41.
Coomans EM, Schoonhoven DN, Tuncel H, Verfaillie SCJ, Wolters EE, Boellaard R, et al. In vivo tau pathology is associated with synaptic loss and altered synaptic function. Alzheimers Res. Ther. 2021;13:35. doi: 10.1186/s13195-021-00772-0
D’Mello C, Swain MG. Immune-to-brain communication pathways in inflammation-associated sickness and depression. Inflammation-Associated Depression: Evidence, Mechanisms and Implications. 2016:73-94.
Dietrich T, Sharma P, Walter C, Weston P, Beck J. The epidemiological evidence behind the association between periodontitis and incident atherosclerotic cardiovascular disease. Journal of clinical periodontology. 2013;40:S70-84.
D'Mello C, Le T, Swain MG. Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factorα signaling during peripheral organ inflammation. Journal of Neuroscience. 2009;29(7):2089-102.
Doifode T, Giridharan VV, Generoso JS, Bhatti G, Collodel A, Schulz PE, et al. The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology. Pharmacological Research. 2021;164:105314.
Dominy SS, Lynch C, Ermini F, Benedyk M, Marczyk A, Konradi A, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science advances. 2019;5(1):eaau3333.
Dominy SS, Lynch C, Ermini F, Benedyk M, Marczyk A, Konradi A, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science advances. 2019;5(1):eaau3333.
Dominy SS, Lynch C, Ermini F, Benedyk M, Marczyk A, Konradi A, Nguyen M, Haditsch U, Raha D, Griffin C, Holsinger LJ. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science advances. 2019 Jan 23;5(1):eaau3333.
Dunn N, Mullee M, Perry VH, Holmes C. Association between dementia and infectious disease: Evidence from a case-control study. Alzheimer Dis. Assoc. Disord. 2005, 19, 91–94.
Giil LM, Midttun Ø, Refsum H, Ulvik A, Advani R, SmithAD, et al. Kynurenine pathway metabolites in Alzheimer’s disease. JAlzheimersDis. 2017;60(2):495–504.
Gmiterek A, Wójtowicz H, Mackiewicz P, Radwan-Oczko M, Kantorowicz M, Chomyszyn-Gajewska M, et al. The unique hmuY gene sequence as a specific marker of Porphyromonas gingivalis. PLoS One. 2013;8(7):e67719.
Grenier D, Imbeault S, Plamondon P, Grenier G, Nakayama K, Mayrand D. Role of gingipains in growth of Porphyromonas gingivalis in the presence of human serum albumin. Infect Immun. 2001 Aug;69(8):5166-72. doi: 10.1128/IAI.69.8.5166-5172.2001. PMID: 11447200; PMCID: PMC98614.
Grenier D, Roy S, Chandad F, Plamondon P, Yoshioka M, Nakayama K, et al. Effect of inactivation of the Arg- and/or Lys-gingipain gene on selected virulence and physiological properties of Porphyromonas gingivalis. Infect. Immun. 2003; 71, 4742–4748.
Griffen AL, Beall CJ, Campbell JH, et al. Distinct and complex bacterial profiles in human periodontitis and health revealed by 16S pyrosequencing. ISME J. 2012;6:1176-1185.
Griffen AL, Becker MR, Lyons SR, Moeschberger ML, Leys EJ. Prevalence of Porphyromonas gingivalis and periodontal health status. Journal of clinical microbiology. 1998;36(11):3239-42.
Gui MJ, Dashper SG, Slakeski N, Chen YY, Reynolds EC. Spheres of influence: Porphyromonas gingivalis outer membrane vesicles. Molecular oral microbiology. 2016;31(5):365-78.
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. Periodontology 2000. 2010;54(1):15.
Haditsch U, Roth T, Rodriguez L, Hancock S, Cecere T, Nguyen M, Arastu-Kapur S, Broce S, Raha D, Lynch CC, Holsinger LJ. Alzheimer’s disease-like neurodegeneration in Porphyromonas gingivalis infected neurons with persistent expression of active gingipains. Journal of Alzheimer's Disease. 2020 Jan 1;75(4):1361-76.
Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends Immunol. 2014;35: 3-11.
Hashioka S, Inoue K, Miyaoka T, Hayashida M, Wake R, Oh-Nishi A, Inagaki M. The possible causal link of periodontitis to neuropsychiatric disorders: more than psychosocial mechanisms. International journal of molecular sciences. 2019 Jul 30;20(15):3723.
He J, Li Y, Cao Y, Xue J, Zhou X. The oral microbiome diversity and its relation to human diseases. Folia microbiologica. 2015;60(1):69-80.
Hoozemans JJ, Veerhuis R, Rozemuller AJ, Eikelenboom P. Non-steroidal anti-inflammatory drugs and cyclooxygenase in Alzheimer's disease. Current Drug Targets. 2003 Aug 1;4(6):461-8.
Hwang I, Oh H, Santo E, Kim DY, Chen JW, Bronson RT, et al. FOXO protects against age‐progressive axonal degeneration. Aging cell. 2018;17(1):e12701.
Ishida N, Ishihara Y, Ishida K, Tada H, Funaki-Kato Y, Hagiwara M, Ferdous T, Abdullah M, Mitani A, Michikawa M, Matsushita K. Periodontitis induced by bacterial infection exacerbates features of Alzheimer’s disease in transgenic mice. npj Aging and Mechanisms of Disease. 2017 Nov 6;3(1):1-7.
Iwasaki M, Kimura Y, Ogawa H, Yamaga T, Ansai T, Wada T, Sakamoto R, Ishimoto Y, Fujisawa M, Okumiya K, Miyazaki H, Matsubayashi K. Periodontitis, periodontal inflammation, and mild cognitive impairment: A 5-year cohort study. J Periodontal Res. 2019;54(3):233-240.
Jia L, Quan M, Fu Y, Zhao T, Li Y, Wei C, et al. Dementia in China: epidemiology, clinical management, and research advances. Lancet Neurol.2020; 19, 81–92. doi: 10.1016/S1474-4422(19)30290-X
Jo S, Kang W, Hwang YS, Lee SH, Park KW, Kim MS, Lee H, Yoon HJ, Park YK, Chalita M, Lee JH. Oral and gut dysbiosis leads to functional alterations in Parkinson’s disease. npj Parkinson's Disease. 2022 Jul 7;8(1):1-2.
Jungbauer G, Stähli A, Zhu X, Auber Alberi L, Sculean A, Eick S. Periodontal microorganisms and Alzheimer disease–A causative relationship?. Periodontology 2000. 2022 Jun;89(1):59-82.
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 & Dementia. 2008;4(4):242-50.
Kamer AR, Pirraglia E, Tsui W, Rusinek H, Vallabhajosula S, Mosconi L, et al. Periodontal disease associates with higher brain amyloid load in normal elderly. Neurobiol Aging. 2015;36:627-633.
Kato Y, Hagiwara M, Ishihara Y, Isoda R, Sugiura S, Komatsu T, Ishida N, et al. TNF-α augmented Porphyromonas gingivalis invasion in human gingival epithelial cells through Rab5 and ICAM-1. BMC microbiology. 2014;14(1):1-3.
Kim S, Shin SJ, Park YH, Nam Y, Kim SM, Jung ID, Yang HD, Park YM, Moon M. Gram-negative bacteria and their lipopolysaccharides in Alzheimer’s disease: pathologic roles and therapeutic implications. Translational Neurodegeneration. 2021 Dec;10(1):1-23.
Könönen E, Gursoy M, Gursoy UK. Periodontitis: a multifaceted disease of tooth-supporting tissues. Journal of clinical medicine. 2019 Jul 31;8(8):1135.
Koyama A, O'Brien J, Weuve J, Blacker D, Metti AL, Yaffe K. The role of peripheral inflammatory markers in dementia and Alzheimer's disease: a meta-analysis. J Gerontol A Biol Sci Med Sci. 2013;68(4):433-440.
Lai KS, Liu CS, Rau A, Lanctôt KL, Köhler CA, Pakosh M, et al. Peripheral inflammatory markers in Alzheimer’s disease: a systematic review and meta-analysis of 175 studies. Journal of Neurology, Neurosurgery & Psychiatry. 2017;88(10):876-82.
Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur. J. Neurol. 2018; 25, 59–70.
Lauretti E, Dincer O, Praticò D. Glycogen synthase kinase-3 signaling in Alzheimer's disease. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2020;1867(5):118664.
Leblhuber F, Strasser B, Steiner K, Gostner J, Schuetz B, Fuchs D. On the role of intestinal microbiota in patients with cognitivedecline. JPharmPharmacol. 2017;5:648–53.
Lee JW, Lee YK, Yuk DY, Choi DY, Ban SB, Oh KW, et al. Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. Journal of neuroinflammation. 2008;5(1):1-4.
Li N, Collyer CA. Gingipains from Porphyromonas gingivalis—complex domain structures confer diverse functions. European Journal of Microbiology and Immunology. 2011 Mar 1;1(1):41-58.
Liccardo D, Marzano F, Carraturo F, Guida M, Femminella GD, Bencivenga L, et al. Potential bidirectional relationship between periodontitis and Alzheimer’s Disease. Front. Physiol. 2020; 11:683. doi: 10.3389/fphys.2020.00683
Lim A, Krajina K, Marsland AL. Peripheral inflammation and cognitive aging. Inflammation in psychiatry. 2013;28:175-87.
Liu Y, Wu Z, Zhang X, Ni J, Yu W, Zhou Y, et al. Leptomeningeal cells transduce peripheral macrophages inflammatory signal to microglia in reponse to Porphyromonas gingivalis LPS. Mediators of Inflammation. 2013;407562.
Maitre Y, Mahalli R, Micheneau P, Delpierre A, Guerin M, Amador G, et al. Pre and Probiotics Involved in the Modulation of Oral Bacterial Species: New Therapeutic Leads in Mental Disorders?. Microorganisms. 2021;9(7):1450.
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. Clinical oral investigations. 2018 Sep;22(7):2463-74.
Malekzadeh S, Edalatmanesh MA, Mehrabani D, Shariati M. Drugs induced Alzheimer’s disease in animal model. Galen Medical Journal, 2017; 6(3), 185-196.
Malekzadeh S, Edalatmanesh MA, Mehrabani D, Shariati M. Effect of the Xenograft Transplantation of Human Dental Pulp Stem Cells on Anxiety and Memory in Trimethyltin Induced-Alzheimer Disease Model. Qom University of Medical Sciences Journal, 2019; 13(7), 10-21.
Malekzadeh S, Edalatmanesh MA, Mehrabani D, Shariati M. Human Dental Pulp Stem Cell Transplantation Improves Passive Avoidance Memory, Neuroinflammation and Hippocampal Histopathology in Trimethyltin-Induced Alzheimer’s Disease Rat Model. Galen Medical Journal, 2021; 10, e2254-e2254.
Manconi B, Liori B, Cabras T, Vincenzoni F, Iavarone F, Castagnola M, Messana I, Olianas A. Salivary cystatins: Exploring new post-translational modifications and polymorphisms by top-down high-resolution mass spectrometry. J Proteome Res. 2017; 16, 4196-4207.
Mao S, Huang CP, Lan H, Lau HG, Chiang CP, Chen YW. Association of periodontitis and oral microbiomes with Alzheimer’s disease: A narrative systematic review. Journal of Dental Sciences. 2022 Jul 21.
Matsushita K, Yamada-Furukawa M, Kurosawa M, Shikama Y. Periodontal disease and periodontal disease-related bacteria involved in the pathogenesis of Alzheimer’s disease. Journal of inflammation research. 2020;13:275.
McGeer PL, Guo JP, Lee M, Kennedy K, McGeer EG. Alzheimer’s disease can be spared by nonsteroidal anti-inflammatory drugs. Journal of Alzheimer's Disease. 2018;62(3):1219-22.
McGeer PL, Schulzer M, McGeer EG. Arthritis and anti inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology. 1996;47 (2):425–432. doi:10.1212/WNL.47.2.425
Naorungroj S, Schoenbach VJ, Wruck L, Mosley TH, Gottesman RF, Alonso A, Heiss G, Beck J, Slade GD. Tooth loss, periodontal disease, and cognitive decline in the Atherosclerosis Risk in Communities (ARIC) study. Community Dent Oral Epidemiol. 2015;43(1):47-57.
Nazir MA. Prevalence of periodontal disease, its association with systemic diseases and prevention. International journal of health sciences. 2017 Apr;11(2):72.
Nie R, Wu Z, Ni J, Zeng F, Yu W, Zhang Y, et al. Porphyromonas gingivalis infection induces amyloid-β accumulation in monocytes/macrophages. J Alzheimer’s Dis. 2019; 72:479–94. doi: 10.3233/JAD-190298
Noble JM, Borrell LN, Papapanou PN, Elkind MS, Scarmeas N, Wright CB. Periodontitis is associated with cognitive impairment among older adults: analysis of NHANES-III. Journal of Neurology, Neurosurgery & Psychiatry. 2009;80(11):1206-11.
Noble JM, Borrell LN, Papapanou PN, Elkind MSV, Scarmeas N, Wright CB. Periodontitis is associated with cognitive impairment among older adults: analysis of NHANES-III. J Neurol Neurosurg Psychiatry. 2009; 80:1206–11. doi: 10.1136/jnnp.2009.174029
Nonaka S, Kadowaki T, Nakanishi H. Secreted gingipains from Porphyromonas gingivalis increase permeability in human cerebral microvascular endothelial cells through intracellular degradation of tight junction proteins. Neurochem Int. 2022 Mar;154:105282. doi: 10.1016/j.neuint.2022.105282. Epub 2022 Jan 13. PMID: 35032577.
Okamoto N, Morikawa M, Tomioka K, Yanagi M, Amano N, Kurumatani N. Association between tooth loss and the development of mild memory impairment in the elderly: the Fujiwara-kyo Study. Journal of Alzheimer's Disease. 2015;44(3):777-86.
Okihara H, Ito JI, Kokai S, Ishida T, Hiranuma M, Kato C, et al. Liquid diet induces memory impairment accompanied by a decreased number of hippocampal neurons in mice. Journal of Neuroscience Research. 2014;92(8):1010-7.
Olsen I, Singhrao SK. Can oral infection be a risk factor for Alzheimer's disease?. Journal of oral microbiology. 2015;7(1):29143.
Olsen I, Singhrao SK. Interaction between genetic factors, Porphyromonas gingivalis and microglia to promote Alzheimer’s disease. Journal of oral microbiology. 2020 Jan 1;12(1):1820834.
Oue H, Miyamoto Y, Koretake K, Okada S, Doi K, Jung CG, et al. Tooth loss might not alter molecular pathogenesis in an aged transgenic Alzheimer's disease model mouse. Gerodontology. 2016;33(3):308-14.
Oue H, Miyamoto Y, Okada S, Koretake K, Jung CG, Michikawa M, et al. Tooth loss induces memory impairment and neuronal cell loss in APP transgenic mice. Behavioural brain research. 2013;252:318-25.
Perera M, Al-Hebshi NN, Speicher DJ, Perera I, Johnson NW. Emerging role of bacteria in oral carcinogenesis: a review with special reference to perio-pathogenic bacteria. Journal of oral microbiology. 2016;8(1):32762.
Plas M, Hemmer PHJ, Been LB, van Ginkel RJ, de Bock GH, van Leeuwen BL. Incidence and predictors of postoperative delirium after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2018;117(2):260-268.
Portelius E, Zetterberg H, Dean RA, Marcil A, Bourgeois P, Nutu M, et al. Amyloid-β 1-15/16 as a Marker for γ-Secretase Inhibition in Alzheimer's Disease. Journal of Alzheimer's Disease. 2012;31(2):335-41.
Raha D, Broce S, Haditsch U, Rodriguez L, Ermini F, Detke M, et al. COR388, a novel gingipain inhibitor, decreases fragmentation of APOE in the central nervous system of Alzheimer’s disease patients: Human/Human trials: Other. Alzheimer's & Dementia. 2020;16:e040578.
Rajmohan R, Reddy PH. Amyloid-beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer’s disease neurons. Journal of Alzheimer's Disease. 2017 Jan 1;57(4):975-99.
Riviere GR, Riviere KH, Smith KS. Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer's disease. Oral microbiology and immunology. 2002;17(2):113-8.
Rogers J, Webster S, Lue LF, Brachova L, Civin WH, Emmerling M, Shivers B, Walker D, McGeer P. Inflammation and Alzheimer's disease pathogenesis. Neurobiology of aging. 1996 Sep 1;17(5):681-6.
Rojanathammanee L, Floden AM, Manocha GD, Combs CK. Attenuation of microglial activation in a mouse model of Alzheimer’s disease via NFAT inhibition. J Neuroinflammation. 2015;12(1):42. doi:10.1186/s12974-015-0255-2
Ryder MI. Porphyromonas gingivalis and Alzheimer disease: Recent findings and potential therapies. Journal of periodontology. 2020;91:S45-9.
Sheldon JR, Laakso HA, Heinrichs DE. Iron acquisition strategies of bacterial pathogens. Microbiology spectrum. 2016 Mar 18;4(2):4-2.
Soukos NS, Stultz J, Abernethy AD, Goodson JM. Phototargeting human periodontal pathogens in vivo. Lasers in medical science. 2015;30(3):943-52.
Sparks Stein P, Steffen MJ, Smith C, Jicha G, Ebersole JI Abner E, et al. Serumantibodies to periodontal pathogens areariskfactorforAlzheimer’sdisease. AlzheimersDement. 2012;8(3):196–203.
Sparks Stein P, Steffen MJ, Smith C, Jicha G, Ebersole JL, Abner E, et al. Serumantibodies to periodontal pathogens are a risk factor for Alzheimer’s disease. Alzheimer’s Dement. 2012; 8:196–203. doi: 10.1016/j.jalz.2011.04.006
Spudich SS, Nilsson AC, Lollo ND, Liegler TJ, Petropoulos CJ, Deeks SG, et al. Cerebrospinal fluid HIV infection and pleocytosis: relation to systemic infection and antiretroviral treatment. BMC infectious diseases. 2005;5(1):1-9.
Stein PS, Steffen MJ, Smith C, Jicha G, Ebersole JL, Abner E, Dawson III D. Serum antibodies to periodontal pathogens are a risk factor for Alzheimer’s disease. Alzheimer's & Dementia. 2012;8(3):196-203.
Stein PS, Steffen MJ, Smith C, Jicha G, Ebersole JL, Abner E, et al. Serum antibodies to periodontal pathogens are a risk factor for Alzheimer’s disease. Alzheimer's & Dementia. 2012;8(3):196-203.
Stewart R, Sabbah W, Tsakos G, D'Aiuto F, Watt RG. Oral health and cognitive function in the Third National Health and Nutrition Examination Survey (NHANES III). Psychosom Med. 2008;70(8):936-941.
Stewart R, Weyant RJ, Garcia ME, Harris T, Launer LJ, Satterfield S, et al. Adverse oral health and cognitive decline: the health, aging and body composition study. Journal of the American Geriatrics Society. 2013;61(2):177-84.
Tiisanoja A, Syrjälä AM, Tertsonen M, Komulainen K, Pesonen P, Knuuttila M, et al. Oral diseases and inflammatory burden and Alzheimer's disease among subjects aged 75 years or older. Special Care in Dentistry. 2019;39(2):158-65.
Tonetti MS, Van Dyke TE, Working Group 1 of the Joint EFP/AAP Workshop. Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. Journal of Clinical Periodontology. 2013;40:S24-9.
Uddin MS, Mamun AA, Takeda S, Sarwar MS, Begum MM. Analyzing the chance of developing dementia among geriatric people: a cross‐sectional pilot study in Bangladesh. Psychogeriatrics. 2019 Mar;19(2):87-94.
Wu C-C, Chu H-W, Hsu C-W, Chang K-P, Liu H-P. Saliva proteome profiling reveals potential salivarybiomarkers for detection of oral cavity squamous cell carcinoma. Proteomics. 2015;15, 3394-3404.
Wu Z, Zhang J, Nakanishi H. Leptomeningeal cells activate microglia and astrocytes to induce IL-10 production by releasing pro-inflammatory cytokines during systemic inflammation. Journal of neuroimmunology. 2005;167(1-2):90-8.
Xuan Y, Gao Y, Huang H, Wang X, Cai Y, Luan QX. Tanshinone IIA attenuates atherosclerosis in apolipoprotein E knockout mice infected with Porphyromonas gingivalis. Inflammation. 2017 Oct;40(5):1631-42.
Yamamoto Y. PCR in diagnosis of infection: detection of bacteria in cerebrospinal fluids. Clinical and Vaccine Immunology. 2002;9(3):508-14.
Yu Y, Yang Y, Tan H, Boukhali M, Khatri A, Yu Y, et al. Tau contributes to sevoflurane-induced neurocognitive impairment in neonatal mice. Anesthesiology. 2020; 133, 595–610. doi: 10.1097/ALN.0000000000003452
Zhang J, Yu C, Zhang X, Chen H, Dong J, Lu W, et al. Porphyromonas gingivalis lipopolysaccharide induces cognitive dysfunction, mediated by neuronal inflammation via activation of the TLR4 signaling pathway in C57BL/6 mice. Journal of neuroinflammation. 2018;15(1):1-4.
Zhang, J., Yu, C., Zhang, X., Chen, H., Dong, J., Lu, W., Song, Z. and Zhou, W., 2018. Porphyromonas gingivalis lipopolysaccharide induces cognitive dysfunction, mediated by neuronal inflammation via activation of the TLR4 signaling pathway in C57BL/6 mice. Journal of neuroinflammation, 15(1), pp.1-14.
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Nigerian Journal of Physiological Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
