scholarly journals Porphyromonas gingivalis (W83) Infection Induces Alzheimer’s Disease-Like Pathophysiology in Obese and Diabetic Mice

2021 ◽  
pp. 1-17
Author(s):  
Bojlul Bahar ◽  
Shalini Kanagasingam ◽  
Murtaza M. Tambuwala ◽  
Alaa A.A. Aljabali ◽  
Stephanie A. Dillon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Periodontal Disease ◽  
Porphyromonas Gingivalis ◽  
Oral Infection ◽  
Silver Impregnation ◽  
Membrane Receptors ◽  
Mrna Abundance ◽  
Co Morbidity ◽  
Porphyromonas Gingivalis W83

Background: Periodontal disease(s) and metabolic illnesses negatively impact the quality of life and, eventually mental health. Objective: This study investigated the effect of Porphyromonas gingivalis (W83) oral infection on the development of Alzheimer’s disease (AD) pathophysiology in a wild-type obese, diabetic (db/db) mouse model. Methods: The db/db mice were either orally infected with P. gingivalis and Fusobacterium nucleatum or sham infected for 16 weeks. The presence of amyloid-β (Aβ) and neurofibrillary tangles (NFTs) were assessed using a silver impregnation technique and subsequently by immunohistochemistry for tau and neuroinflammation. The mRNA abundance of a panel of 184 genes was performed using quantitative real-time PCR, and the differentially expressed genes were analyzed by Ingenuity Pathway Analysis. Results: While no Aβ plaques and NFTs were evident by silver impregnation, immunohistochemistry (glial cell markers) of the P. gingivalis-infected mice tissue sections exhibited neuroinflammation in the form of reactive microglia and astrocytes. Anti-tau immunopositivity, in addition to cells, was prominent in thickened axons of hippocampal CA neurons. The mRNA abundance of crucial genes in the insulin signaling pathway (INSR, IGF1, IRS, IDE, PIK3R, SGK1, GYS, GSK3B, AKT1) were upregulated, potentially exacerbating insulin resistance in the brain by P. gingivalis oral infection. Increased mRNA abundance of several kinases, membrane receptors, transcription factors, and pro-inflammatory mediators indicated hyperactivation of intracellular cascades with potential for tau phosphorylation and Aβ release in the same infection group. Conclusion: P. gingivalis W83 infection of db/db mice provides a disease co-morbidity model with the potential to reproduce AD pathophysiology with induced periodontal disease.

scholarly journals Emerging evidence for associations between periodontitis and the development of Alzheimer’s disease

2014 ◽  
Vol 5 (1) ◽  
pp. 38-42 ◽  
Author(s):  
Sophie Poole ◽  
Sim K Singhrao ◽  
St John Crean
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Immune Responses ◽  
Periodontal Disease ◽  
Potential Risk ◽  
Inflammatory Disease ◽  
Pathogenic Bacteria ◽  
Late Onset ◽  
Systemic Circulation

Periodontal disease (PD) is an inflammatory disease affecting tooth-supporting tissues in which interaction of specific bacteria and the host’s immune responses play a pivotal role. The pathogenic bacteria associated with PD are a source of systemic inflammation as they have the ability to enter systemic circulation during everyday tasks such as brushing teeth and chewing food. Alzheimer’s disease (AD) is a form of dementia whereby inflammation is thought to play a key role in its pathogenesis and the risk of developing the disease increasing with age. The exact aetiology of the late-onset AD is unknown but peripheral infections are being considered as a potential risk factor.

scholarly journals Potential Role of Phosphoglycerol Dihydroceramide Produced by Periodontal Pathogen Porphyromonas gingivalis in the Pathogenesis of Alzheimer’s Disease

2020 ◽  
Vol 11 ◽  
Author(s):  
Chiaki Yamada ◽  
Juliet Akkaoui ◽  
Anny Ho ◽  
Carolina Duarte ◽  
Richard Deth ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Porphyromonas Gingivalis ◽  
Virulence Factors ◽  
Potential Role ◽  
Sirtuin 1 ◽  
Periodontal Pathogen ◽  
Secretory Phenotype ◽  
Aβ42 Peptide

BackgroundAmong different types of sphingolipids produced by human cells, the possible engagement of ceramide species in the pathogenesis of Alzheimer’s disease (AD) has attracted recent attention. While ceramides are primarily generated by de novo synthesis in mammalian cells, only a limited number of bacterial species, produce ceramides, including phosphoglycerol dihydroceramide (PGDHC) that is produced by the key periodontal pathogen Porphyromonas gingivalis. Emerging evidence indicates that virulence factors produced by P. gingivalis, such as lipopolysaccharide and gingipain, may be engaged in the initiation and/or progression of AD. However, the potential role of PGDHC in the pathogenesis of AD remains unknown. Therefore, the aim of this study was to evaluate the influence of PGDHC on hallmark findings in AD.Material and MethodsCHO-7WD10 and SH-SY-5Y cells were exposed to PGDHC and lipopolysaccharide (LPS) isolated from P. gingivalis. Soluble Aβ42 peptide, amyloid precursor protein (APP), phosphorylated tau and senescence-associated secretory phenotype (SASP) factors were quantified using ELISA and Western blot assays. ResultsOur results indicate that P. gingivalis (Pg)-derived PGDHC, but not Pg-LPS, upregulated secretion of soluble Aβ42 peptide and expression of APP in CHO-7WD10 cells. Furthermore, hyperphosphorylation of tau protein was observed in SH-SY-5Y cells in response to PGDHC lipid. In contrast, Pg-LPS had little, or no significant effect on the tau phosphorylation induced in SH-SY-5Y cells. However, both PGDHC and Pg-LPS contributed to the senescence of SH-SY5Y cells as indicated by the production of senescence-associated secretory phenotype (SASP) markers, including beta-galactosidase, cathepsin B (CtsB), and pro-inflammatory cytokines TNF-α, and IL-6. Additionally, PGDHC diminished expression of the senescence-protection marker sirtuin-1 in SH-SY-5Y cells.ConclusionsAltogether, our results indicate that P. gingivalis-derived PGDHC ceramide promotes amyloidogenesis and hyperphosphorylation, as well as the production of SASP factors. Thus, PGDHC may represent a novel class of bacterial-derived virulence factors for AD associated with periodontitis.

The Influence of Co-Morbidity and Frailty on the Clinical Manifestation of Patients with Alzheimer's Disease

2014 ◽  
Vol 42 (2) ◽  
pp. 501-509 ◽  
Author(s):  
Saskia M. Oosterveld ◽  
Roy P.C. Kessels ◽  
Renske Hamel ◽  
Inez H.G.B. Ramakers ◽  
Pauline Aalten ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Manifestation ◽  
Co Morbidity

scholarly journals Analysis the Link between Periodontal Diseases and Alzheimer’s Disease: A Systematic Review

2021 ◽  
Vol 18 (17) ◽  
pp. 9312
Author(s):  
Leslie Borsa ◽  
Margaux Dubois ◽  
Guillaume Sacco ◽  
Laurence Lupi
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Periodontal Disease ◽  
Periodontal Diseases ◽  
Fold Increase ◽  
Assessment Tools ◽  
Cochrane Library ◽  
The Cochrane Library

The hypothesis of an infectious connection from the oro-pharyngeal sphere to the brain underlines the interest in analyzing the link between periodontal disease and Alzheimer’s disease. The aim of this systematic review was to examine the link between Alzheimer’s disease and periodontal disease in patients aged 65 and over. Databases (PubMed (MEDLINE), the Cochrane Library, and Embase) were analyzed for relevant references up to 21 June 2021. The authors independently selected the studies and extracted the data. The quality of included studies was checked using the National Institutes of Health’s quality assessment tools. Five studies were included. The selected studies described in their results an increase in F. nucleatum in Alzheimer’s disease patients (adjusted p = 0.02), and its incidence was linked to C. rectus and P. gingivalis (adjusted HR = 1.22 (1.04–1.43), p = 0.012) as well as A. naeslundii (crude HR = 2.0 (1.1–3.8)). The presence of periodontitis at baseline was associated with a six-fold increase in the rate of cognitive decline over a 6-month follow-up period (ADAS-Cog mean change = 2.9 ± 6.6). The current review suggests an association between periodontal disease and Alzheimer’s disease. The treatment of periodontal disease could be a way to explore Alzheimer’s disease prevention.

scholarly journals Characterization of Human Genes Modulated by Porphyromonas gingivalis Highlights the Ribosome, Hypothalamus, and Cholinergic Neurons

2021 ◽  
Vol 12 ◽  
Author(s):  
Sejal Patel ◽  
Derek Howard ◽  
Nityananda Chowdhury ◽  
Casey Derieux ◽  
Bridgette Wellslager ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Porphyromonas Gingivalis ◽  
Protein Targeting ◽  
Expression Patterns ◽  
Cholinergic Neurons ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Human Genes ◽  
Lysine Residues

Porphyromonas gingivalis, a bacterium associated with periodontal disease, is a suspected cause of Alzheimer’s disease. This bacterium is reliant on gingipain proteases, which cleave host proteins after arginine and lysine residues. To characterize gingipain susceptibility, we performed enrichment analyses of arginine and lysine proportion proteome-wide. Genes differentially expressed in brain samples with detected P. gingivalis reads were also examined. Genes from these analyses were tested for functional enrichment and specific neuroanatomical expression patterns. Proteins in the SRP-dependent cotranslational protein targeting to membrane pathway were enriched for these residues and previously associated with periodontal and Alzheimer’s disease. These ribosomal genes are up-regulated in prefrontal cortex samples with detected P. gingivalis sequences. Other differentially expressed genes have been previously associated with dementia (ITM2B, MAPT, ZNF267, and DHX37). For an anatomical perspective, we characterized the expression of the P. gingivalis associated genes in the mouse and human brain. This analysis highlighted the hypothalamus, cholinergic neurons, and the basal forebrain. Our results suggest markers of neural P. gingivalis infection and link the cholinergic and gingipain hypotheses of Alzheimer’s disease.

scholarly journals Periodontal disease exacerbates Alzheimer's disease

2018 ◽  
Vol 60 (3) ◽  
pp. 147-152
Author(s):  
Naoyuki Ishida ◽  
Nobuo Yoshinari ◽  
Kenji Matsushita ◽  
Yuichi Ishihara
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Periodontal Disease

scholarly journals Alzheimer’s Disease-Like Pathology Triggered by Porphyromonas gingivalis in Wild Type Rats Is Serotype Dependent

2020 ◽  
Vol 11 ◽  
Author(s):  
Jaime Díaz-Zúñiga ◽  
Jamileth More ◽  
Samanta Melgar-Rodríguez ◽  
Matías Jiménez-Unión ◽  
Francisca Villalobos-Orchard ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Porphyromonas Gingivalis ◽  
Wild Type
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