Is Periodontal Disease Associated with Alzheimer's Disease? A Systematic Review with Meta-Analysis

Leira, Yago; Domínguez, Carlos; Seoane, Juan; Seoane-Romero, Juan M.; Pías‐Peleteiro, Juan Manuel; Takkouche, Bahi; Blanco, Juan; Aldrey, José Manuel

doi:10.1159/000458411

Cited by 97 publications

(82 citation statements)

References 45 publications

(73 reference statements)

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“…ApoE fragmentation has been extensively studied in relation to Alzheimer's disease; therefore, it could be worth mentioning that P. gingivalis has been shown to be able to invade the brain, and possibly the gingipain‐induced proteolysis of lipoproteins may be a mechanism involved in the local atherogenic process and in the degenerating brain as well. Furthermore, several studies have reported a link between periodontitis and Alzheimer's disease …”

Section: Discussionmentioning

confidence: 99%

Lipoprotein modifications by gingipains of Porphyromonas gingivalis

Lönn

Ljunggren

Klarström-Engström

et al. 2018

J of Periodontal Research

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Background and ObjectiveSeveral studies have shown an association between periodontitis and cardiovascular disease (CVD). Atherosclerosis is the major cause of CVD, and a key event in the development of atherosclerosis is accumulation of lipoproteins within the arterial wall. Bacteria are the primary etiologic agents in periodontitis and Porphyromonas gingivalis is the major pathogen in the disease. Several studies support a role of modified low‐density lipoprotein (LDL) in atherogenesis; however, the pathogenic stimuli that induce the changes and the mechanisms by which this occur are unknown. This study aims to identify alterations in plasma lipoproteins induced by the periodontopathic species of bacterium, P. gingivalis, in vitro.Material and MethodsPlasma lipoproteins were isolated from whole blood treated with wild‐type and gingipain‐mutant (lacking either the Rgp‐ or Kgp gingipains) P. gingivalis by density/gradient‐ultracentrifugation and were studied using 2‐dimensional gel electrophoresis followed by matrix‐assisted laser desorption/ionization mass spectrometry. Porphyromonas gingivalis‐induced lipid peroxidation and antioxidant levels were measured by thiobarbituric acid‐reactive substances and antioxidant assay kits, respectively, and lumiaggregometry was used for measurement of reactive oxygen species (ROS) and aggregation.Results Porphyromonas gingivalis exerted substantial proteolytic effects on the lipoproteins. The Rgp gingipains were responsible for producing 2 apoE fragments, as well as 2 apoB‐100 fragments, in LDL, and the Kgp gingipain produced an unidentified fragment in high‐density lipoproteins. Porphyromonas gingivalis and its different gingipain variants induced ROS and consumed antioxidants. Both the Rgp and Kgp gingipains were involved in inducing lipid peroxidation.Conclusion Porphyromonas gingivalis has the potential to change the expression of lipoproteins in blood, which may represent a crucial link between periodontitis and CVD.

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Section: Discussionmentioning

confidence: 99%

Lipoprotein modifications by gingipains of Porphyromonas gingivalis

Lönn

Ljunggren

Klarström-Engström

et al. 2018

J of Periodontal Research

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“…tooth loss) have been associated with cognitive decline/impairment in patients with AD (Holmer, Eriksdotter, Schultzberg, Pussinen, & Buhlin, ; Ide et al, ; Takeuchi et al, ). A recent meta‐analysis of observational studies showed that subjects diagnosed with periodontitis have a 1.6‐fold increased risk of developing AD (Leira et al, ). We recently demonstrated that bacterial endotoxin (i.e.…”

Section: Introductionmentioning

confidence: 99%

Periodontitis and systemic markers of neurodegeneration: A case–control study

Leira

Carballo

Orlandi

et al. 2020

J Clinic Periodontology

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Aim:To investigate whether periodontitis is associated with amyloid beta (Aβ) peptides and whether systemic inflammation could act as a potential mediator of this link. Materials and Methods:A case-control study was designed including 75 patients with periodontitis (cases) and 75 age-balanced and gender-matched participants without periodontitis (controls). Full-mouth periodontal evaluation was performed in all participants. Demographic, clinical and behaviour data were also recorded. Fasting blood samples were collected, and serum levels of interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), Aβ 1-40 and Aβ 1-42 were determined.Results: Cases showed higher levels of IL-6 (8.7 ± 3.2 vs. 4.8 ± 0.5 pg/ml), hs-CRP (3.3 ± 1.2 vs. 0.9 ± 0.7 mg/L), Aβ 1-40 (37.3 ± 6.0 vs. 30.3 ± 1.8 pg/ml) and Aβ 1-42 (54.5 ± 10.6 vs. 36.5 ± 10.0 pg/ml) when compared to controls (all p < .001). Diagnosis of periodontitis was statistically significantly associated with cir-culating Aβ 1-40 ( coefficient adjusted = 6.9, 95% CI: 5.4-8.3; p < .001) and Aβ ( coefficient adjusted = 17.8, 95% CI: 14.4-21.3; p < .001). Mediation analysis confirmed hs-CRP and IL-6 as mediators of this association. Conclusions:Periodontitis is associated with increased peripheral levels of Aβ. This finding could be explained by enhanced systemic inflammation that can be seen in patients with periodontitis.

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“…Recent systematic reviews suggest that older people with dementia have multiple oral health problems (Delwel et al, 2018;Gusman et al, 2018;Leira et al, 2017;Maldonado, Laugisch, Burgin, Sculean, & Eick, 2018). However, studies on the relationship between periodontitis and cognitive decline are few but indicate an association (Gil-Montoya et al, 2014;Syrjala et al, 2012;Zenthofer et al, 2017).…”

Section: Introductionmentioning

confidence: 99%