Int J Stomatol ›› 2022, Vol. 49 ›› Issue (4): 397-403.doi: 10.7518/gjkq.2022074

• Oral Microbiology • Previous Articles     Next Articles

Research progress on the role of Porphyromonas gingivalis on promoting the development of Alzheimer ’ s disease

Wang Guanru(),Feng Qiang.()   

  1. Dept. of Human Microbiome, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory of Dental Materials and Oral Tissue Regeneration, Jinan 250012, China
  • Received:2021-10-12 Revised:2022-03-16 Online:2022-07-01 Published:2022-06-28
  • Contact: Qiang. Feng;


Periodontitis is an oral disease with high incidence in middle-aged and elderly individuals. It is also closely related to the increased risk of Alzheimer ’ s disease. Recent studies suggest that Porphyromonas gingivalis (P. gingivalis), the main pathogen of periodontitis, may be one of the pathogenic factors for Alzheimer ’ s disease. The DNA or specific antibodies of P. gingivalis can be detected in the cerebrospinal fluid or serum of patients with Alzheimer ’ s disease. Animal experiments showed that P. gingivalis or its toxic factors, such as lipopolysaccharide, gingival protease and peptidyl arginine deiminase, could reduce the learning and memory ability of mice. P. gingivalis could interfere with the host immune function by releasing a variety of inflammatory mediators, which cause a series of immune inflammatory reactions and destroy the function of host nerve cells. This study systematically reviewed the recent progress of P. gingivalis in the aetiology of Alzheimer ’ s disease to lay a foundation for comprehensively understanding the pathogenesis of Alzheimer ’ s disease.

Key words: Porphyromonas gingivalis, Alzheimer ’ s disease, pathogenesis

CLC Number: 

  • R 782


Fig 1

Potential mechanism of P. gingivalis promoting the occurrence and development of AD"

1 Silva MVF, Loures CMG, Alves LCV, et al. Alzheimer’s disease: risk factors and potentially protective measures[J]. J Biomed Sci, 2019, 26(1): 33.
2 Scheltens P, Blennow K, Breteler MM, et al. Alzheimer’s disease[J]. Lancet, 2016, 388(10043): 505-517.
3 Pritchard AB, Crean S, Olsen I, et al. Periodontitis, microbiomes and their role in Alzheimer’s disease[J]. Front Aging Neurosci, 2017, 9: 336.
4 Breijyeh Z, Karaman R. Comprehensive review on Alzheimer’s disease: causes and treatment[J]. Molecules, 2020, 25(24): 5789.
5 Chen CK, Wu YT, Chang YC. Association between chronic periodontitis and the risk of Alzheimer’s di-sease: a retrospective, population-based, matched-cohort study[J]. Alzheimer’s Res Ther, 2017, 9(1): 56.
6 Nadim R, Tang J, Dilmohamed A, et al. Influence of periodontal disease on risk of dementia: a systema-tic literature review and a meta-analysis[J]. Eur J Epidemiol, 2020, 35(9): 821-833.
7 Leblhuber F, Huemer J, Steiner K, et al. Knock-on effect of periodontitis to the pathogenesis of Alzhei-mer ’ s disease[J]. Wiener Klinische Wochenschrift, 2020, 132(17/18): 493-498.
8 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[J]. Sci Adv, 2019, 5(1): eaau3333.
9 Bennett JP, Keeney PM, Brohawn DG. RNA sequencing reveals small and variable contributions of infectious agents to transcriptomes of postmortem nervous tissues from amyotrophic lateral sclerosis, Alzheimer’s disease and Parkinson’s disease subjects, and increased expression of genes from di-sease-activated microglia[J]. Front Neurosci, 2019, 13: 235.
10 Sparks Stein P, Steffen MJ, Smith C, et al. Serum antibodies to periodontal pathogens are a risk fac-tor for Alzheimer’s disease[J]. Alzheimers Dement, 2012, 8(3): 196-203.
11 Noble JM, Scarmeas N, Celenti RS, et al. Serum IgG antibody levels to periodontal microbiota are associated with incident Alzheimer disease[J]. PLoS One, 2014, 9(12): e114959.
12 Olsen I, Singhrao SK. Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signalling[J]. J Oral Microbiol, 2018, 10(1): 1440128.
13 Wu Z, Ni JJ, Liu YC, et al. Cathepsin B plays a critical role in inducing Alzheimer’s disease-like phenotypes following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis in mice[J]. Brain Behav Immun, 2017, 65: 350-361.
14 Singhrao SK, Olsen I. Are Porphyromonas gingivalis outer membrane vesicles microbullets for spora-dic Alzheimer’s disease manifestation[J] J Alzhei-mers Dis Rep, 2018, 2(1): 219-228.
15 Zhang J, Yu CB, Zhang X, et al. Porphyromonas gingivalis lipopolysaccharide induces cognitive dysfunction, mediated by neuronal inflammation via activation of the TLR4 signaling pathway in C57BL/6 mice[J]. J Neuroinflammation, 2018, 15(1): 37.
16 Olsen I, Singhrao SK. Is there a link between gene-tic defects in the complement cascade and Porphyromonas gingivalis in Alzheimer’s disease[J]. J Oral Microbiol, 2020, 12(1): 1676486.
17 Liu YC, Wu Z, Nakanishi Y, et al. Author Correction: infection of microglia with Porphyromonas gingivalis promotes cell migration and an inflammatory response through the gingipain-mediated activation of protease-activated receptor-2 in mice[J]. Sci Rep, 2018, 8(1): 10304.
18 Nonaka S, Nakanishi H. Secreted gingipains from Porphyromonas gingivalis induce microglia migration through endosomal signaling by protease-activa-ted receptor 2[J]. Neurochem Int, 2020, 140: 104840.
19 Potempa M, Potempa J, Okroj M, et al. Binding of complement inhibitor C4b-binding protein contri-butes to serum resistance of Porphyromonas gingivalis [J]. J Immunol, 2008, 181(8): 5537-5544.
20 Arastu-Kapur S, Nguyen M, Raha D, et al. Treatment of Porphyromonas gulae infection and downstream pathology in the aged dog by lysine-gingipain inhibitor COR388[J]. Pharmacol Res Perspect, 2020, 8(1): e00562.
21 McGraw WT, Potempa J, Farley D, et al. Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase[J]. Infect Immun, 1999, 67(7): 3248-3256.
22 Ishigami A, Ohsawa T, Hiratsuka M, et al. Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer’s disease[J]. J Neurosci Res, 2005, 80(1): 120-128.
23 György B, Tóth E, Tarcsa E, et al. Citrullination: a posttranslational modification in health and disease[J]. Int J Biochem Cell Biol, 2006, 38(10): 1662-1677.
24 Ishigami A, Masutomi H, Handa S, et al. Mass spectrometric identification of citrullination sites and immunohistochemical detection of citrullinated glial fibrillary acidic protein in Alzheimer’s disease brains[J]. J Neurosci Res, 2015, 93(11): 1664-1674.
25 Olsen I, Singhrao SK. Interaction between genetic factors, Porphyromonas gingivalis and microglia to promote Alzheimer’s disease[J]. J Oral Microbiol, 2020, 12(1): 1820834.
26 Olsen I, Singhrao SK, Potempa J. Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer’s disease[J]. J Oral Microbiol, 2018, 10(1): 1487742.
27 Meghil MM, Cutler CW. Oral microbes and mucosal dendritic cells, “Spark and Flame” of local and distant inflammatory diseases[J]. Int J Mol Sci, 2020, 21(5): 1643.
28 El-Awady AR, Miles B, Scisci E, et al. Porphyromonas gingivalis evasion of autophagy and intracellular killing by human myeloid dendritic cells involves DC-SIGN-TLR2 crosstalk[J]. PLoS Pathog, 2015, 10(2): e1004647.
29 Dorn BR, Dunn WA, Progulske-Fox A. Porphyromonas gingivalis traffics to autophagosomes in human coronary artery endothelial cells[J]. Infect Immun, 2001, 69(9): 5698-5708.
30 Memedovski Z, Czerwonka E, Han J, et al. Classical and alternative activation of rat microglia treated with ultrapure Porphyromonas gingivalis lipopolysaccharide in vitro [J]. Toxins (Basel), 2020, 12(5): 333.
31 Rong XF, Xiang LP, Li YF, et al. Chronic periodontitis and alzheimer disease: a putative link of serum proteins identification by 2D-DIGE proteomics[J]. Front Aging Neurosci, 2020, 12: 248.
32 Ding Y, Ren JY, Yu HQ, et al. Porphyromonas gingivalis, a periodontitis causing bacterium, induces me-mory impairment and age-dependent neuroinflammation in mice[J]. Immun Ageing, 2018, 15: 6.
33 Ishida N, Ishihara Y, Ishida K, et al. Periodontitis induced by bacterial infection exacerbates features of Alzheimer’s disease in transgenic mice[J]. NPJ A-ging Mech Dis, 2017, 3: 15.
34 Akiyama H, Barger S, Barnum S, et al. Inflammation and Alzheimer’s disease[J]. Neurobiol Aging, 2000, 21(3): 383-421.
35 McGeer PL, McGeer EG. Inflammation, autotoxicity and Alzheimer disease[J]. Neurobiol Aging, 2001, 22(6): 799-809.
36 Liu J, Wang Y, Guo J, et al. Salvianolic acid B improves cognitive impairment by inhibiting neuroinflammation and decreasing Aβ level in Porphyromonas gingivalis-infected mice[J]. Aging (Albany NY), 2020, 12(11): 10117-10128.
37 Shaddox LM, Gonçalves PF, Vovk A, et al. LPS-induced inflammatory response after therapy of aggressive periodontitis[J]. J Dent Res, 2013, 92(8): 702-708.
38 Rajendran M, Looney S, Singh N, et al. Systemic antibiotic therapy reduces circulating inflammatory dendritic cells and treg-Th17 plasticity in periodontitis[J]. J Immunol, 2019, 202(9): 2690-2699.
39 Gaddis DE, Maynard CL, Weaver CT, et al. Role of TLR2-dependent IL-10 production in the inhibition of the initial IFN-γ T cell response to Porphyromo-nas gingivalis [J]. J Leukoc Biol, 2013, 93(1): 21-31.
40 Liccardo D, Marzano F, Carraturo F, et al. Potential bidirectional relationship between periodontitis and Alzheimer’s disease[J]. Front Physiol, 2020, 11: 683.
41 Olsen I. Possible effects of Porphyromonas gingivalis on the blood-brain barrier in Alzheimer’s disease[J]. Expert Rev Anti Infect Ther, 2021, 19(11): 1367-1371.
42 Jaeger LB, Dohgu S, Hwang MC, et al. Testing the neurovascular hypothesis of Alzheimer’s disease: LRP-1 antisense reduces blood-brain barrier clea-rance, increases brain levels of amyloid-beta protein, and impairs cognition[J]. J Alzheimers Dis, 2009, 17(3): 553-570.
43 Zeng F, Liu YC, Huang WY, et al. Receptor for advanced glycation end products up-regulation in cerebral endothelial cells mediates cerebrovascular-rela-ted amyloid β accumulation after Porphyromonas gingivalis infection[J]. J Neurochem, 2021, 158(3): 724-736.
44 Carter CJ, France J, Crean S, et al. The Porphyromonas gingivalis/host interactome shows enrichment in GWASdb genes related to Alzheimer’s disease, diabetes and cardiovascular diseases[J]. Front Aging Neurosci, 2017, 9: 408.
[1] Xia Weiyao,Jia Zhonglin. Research progress on the relationship between vitamin and oral clefts [J]. Int J Stomatol, 2023, 50(6): 632-638.
[2] Lei Bin,Chen Ke. Classification and treatment of dentin dysplasia type[J]. Int J Stomatol, 2022, 49(3): 332-336.
[3] Fu Zhuohui,Tan Xuelian,Huang Dingming. Diagnosis and treatment of odontogenic maxillary sinusitis [J]. Int J Stomatol, 2021, 48(3): 367-372.
[4] Lei Shuang,Yu Jingjun,Tang Xiaolin. Research progress on the effects and mechanisms of Porphyromonas gingivalis on vascular endothelial cells from different tissues [J]. Int J Stomatol, 2021, 48(1): 23-28.
[5] Zhang Zhiying,Liu Dongjuan,Pan Yaping. Research progress on Porphyromonas gingivalis outer membrane vesicles [J]. Int J Stomatol, 2019, 46(6): 670-674.
[6] Zhou Yuxi,Yong Xiangzhi,Jiang Qiaozhi,Tao Renchuan. Oral chronic graft versus host disease [J]. Int J Stomatol, 2019, 46(5): 609-616.
[7] Zheng Zhi, Yan Shiguo. Relationship between herpes virus and periodontitis [J]. Inter J Stomatol, 2018, 45(2): 224-227.
[8] Zhang Feng, Ouyang Shaobo, Liao Lan. Research progress on the pathogenesis of non-syndromic tooth agenesis [J]. Inter J Stomatol, 2018, 45(2): 219-223.
[9] Cheng Xingqun, Xu Xin, Zhou Xuedong, Li Yuqing.. Research progress on cyclic di-adenosine monophosphate signaling system and its potential role in oral bacterial pathogenesis [J]. Inter J Stomatol, 2017, 44(6): 647-653.
[10] Li Sijie1, Xiao Xue2, Zhao Wei1. Research progress on the pathogenesis of ectodermal dysplasia syndrome [J]. Inter J Stomatol, 2017, 44(2): 244-248.
[11] Wei Bin, Sun Guowen. Mechanism and treatment of bisphosphonate-related osteonecrosis of the jaw [J]. Inter J Stomatol, 2016, 43(4): 445-448.
[12] Han Zhiqiang, Bai Yang, Xiao Shuiqing, Sun Fei, He Ping. Influence of Porphyromonas gingivalis and its gingipain K in healthy gingiva of teenagers [J]. Inter J Stomatol, 2016, 43(3): 283-287.
[13] Shi Jing, Yan Zhengbin, Hou Jingqiu, Peng Hui. Influence of bracketless invisible aligner technique and conventional technique on the number of Streptococcus mutans and Porphyromonas gingivalis [J]. Inter J Stomatol, 2016, 43(2): 151-154.
[14] Dai Qingyun, Cui Yuan, Feng Hui, Jiang Lu. Research progress on the etiology and pathogenesis of burning mouth syndrome [J]. Inter J Stomatol, 2015, 42(1): 54-58.
[15] Zhang Beibei 1,Zhao Lijuan 2 ..
Research progress on the mechanisms for the social psychosocial factors and dental caries
[J]. Inter J Stomatol, 2013, 40(2): 245-248.
Full text



[1] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[2] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[3] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[4] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[5] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[6] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[7] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[8] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[9] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[10] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .