Presenting Author

Noah Al-Hassan

Presentation Type

Oral Presentation

Discipline Track

Biomedical Science

Abstract Type

Research/Clinical

Abstract

Background: Periodontal disease (PD), affecting 20-50% of the global population is marked by biofilm-induced inflammation in oral tissues. Chronic PD results in systemic complications such as heart disease, stroke, and Alzheimer's. The red complex microbes, Porphyromonas gingivalis and Treponema denticola, play a pivotal role, penetrating the blood-brain barrier and contributing to neurodegeneration. Alzheimer's disease (AD), an irreversible neurodegenerative disorder, is linked to abnormal protein cleavage and potentially involves microbiologic components, including gram-positive cocci. Research suggests the presence of bacteria such as Porphyromonas, Actinomyces, and Treponema in autopsied AD brains. Investigating the microbiologic connection between PD and AD is crucial, considering the potential neuroanatomic pathways and enhanced neurotropism exhibited by specific microbes. This exploration is vital for identifying interventions that could mitigate the severity of these prevalent global conditions, addressing the substantial burden they impose on the population.

Methods: A comprehensive systematic review from 2010 to 2023 was conducted across electronic databases like PubMed, PLOS ONE, Nature, Springer, and Sage. The search strategy used keywords related to "Porphyromonas gingivalis," "Treponema denticola," "periodontal disease," and “oral pathogens in neurocognitive disorders.” Inclusion criteria considered peer-reviewed English studies investigating the pathogens or the P. gingivalis and T. denticola relationship in Alzheimer's disease (AD), encompassing both in vitro and in vivo research. Excluded were non-peer-reviewed, case reports, reviews, commentaries, and non-English studies. Two independent reviewers screened titles and abstracts, followed by a full-text review of relevant articles. Data extraction included authors, publication year, sample size, methods, findings, tables, figures, and conclusions. The review adhered to PRISMA guidelines, ensuring transparency and comprehensiveness in reporting the research process and findings. Ethical considerations were unnecessary, given the reliance on publicly available data from previously published studies.

Results: Multiple clinical studies establish a link between periodontitis and Alzheimer's disease (AD). Red complex pathogens, P. gingivalis and T. denticola, can move from the oral cavity to the brain through inflammation. T. denticola is associated with increased neuronal apoptosis by down-regulating key proteins combating Aβ accumulation in the hippocampi. Additionally, it may induce Aβ accumulation and cause neuronal apoptosis through mitochondrial pathways. However, further research is needed to confirm this. P. gingivalis can enter the brain, causing inflammation and subsequent neuron degeneration. Both pathogens increase Aβ accumulation in the hippocampi, but P. gingivalis also induces increased production of NFTs and neuron loss.

Conclusions: In conclusion, the collective evidence from multiple clinical studies solidly establishes a compelling link between periodontitis and Alzheimer's disease (AD). The red complex pathogens, namely P. gingivalis and T. denticola, demonstrate a capacity to traverse from the oral cavity to the brain, propelled by inflammation. T. denticola's association with heightened neuronal apoptosis, particularly through the down-regulation of crucial proteins combatting Aβ accumulation in the hippocampi, suggests a potential mechanistic role. Although further research is imperative to corroborate these findings, the observed cognitive impairment in severe periodontitis patients being three times greater than those with mild or no periodontitis suggests that both pathogens, through their synergistic action, exacerbate AD development by enhancing inflammation.

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The Role of Oral Microbiota in Periodontitis and Alzheimer's Disease

Background: Periodontal disease (PD), affecting 20-50% of the global population is marked by biofilm-induced inflammation in oral tissues. Chronic PD results in systemic complications such as heart disease, stroke, and Alzheimer's. The red complex microbes, Porphyromonas gingivalis and Treponema denticola, play a pivotal role, penetrating the blood-brain barrier and contributing to neurodegeneration. Alzheimer's disease (AD), an irreversible neurodegenerative disorder, is linked to abnormal protein cleavage and potentially involves microbiologic components, including gram-positive cocci. Research suggests the presence of bacteria such as Porphyromonas, Actinomyces, and Treponema in autopsied AD brains. Investigating the microbiologic connection between PD and AD is crucial, considering the potential neuroanatomic pathways and enhanced neurotropism exhibited by specific microbes. This exploration is vital for identifying interventions that could mitigate the severity of these prevalent global conditions, addressing the substantial burden they impose on the population.

Methods: A comprehensive systematic review from 2010 to 2023 was conducted across electronic databases like PubMed, PLOS ONE, Nature, Springer, and Sage. The search strategy used keywords related to "Porphyromonas gingivalis," "Treponema denticola," "periodontal disease," and “oral pathogens in neurocognitive disorders.” Inclusion criteria considered peer-reviewed English studies investigating the pathogens or the P. gingivalis and T. denticola relationship in Alzheimer's disease (AD), encompassing both in vitro and in vivo research. Excluded were non-peer-reviewed, case reports, reviews, commentaries, and non-English studies. Two independent reviewers screened titles and abstracts, followed by a full-text review of relevant articles. Data extraction included authors, publication year, sample size, methods, findings, tables, figures, and conclusions. The review adhered to PRISMA guidelines, ensuring transparency and comprehensiveness in reporting the research process and findings. Ethical considerations were unnecessary, given the reliance on publicly available data from previously published studies.

Results: Multiple clinical studies establish a link between periodontitis and Alzheimer's disease (AD). Red complex pathogens, P. gingivalis and T. denticola, can move from the oral cavity to the brain through inflammation. T. denticola is associated with increased neuronal apoptosis by down-regulating key proteins combating Aβ accumulation in the hippocampi. Additionally, it may induce Aβ accumulation and cause neuronal apoptosis through mitochondrial pathways. However, further research is needed to confirm this. P. gingivalis can enter the brain, causing inflammation and subsequent neuron degeneration. Both pathogens increase Aβ accumulation in the hippocampi, but P. gingivalis also induces increased production of NFTs and neuron loss.

Conclusions: In conclusion, the collective evidence from multiple clinical studies solidly establishes a compelling link between periodontitis and Alzheimer's disease (AD). The red complex pathogens, namely P. gingivalis and T. denticola, demonstrate a capacity to traverse from the oral cavity to the brain, propelled by inflammation. T. denticola's association with heightened neuronal apoptosis, particularly through the down-regulation of crucial proteins combatting Aβ accumulation in the hippocampi, suggests a potential mechanistic role. Although further research is imperative to corroborate these findings, the observed cognitive impairment in severe periodontitis patients being three times greater than those with mild or no periodontitis suggests that both pathogens, through their synergistic action, exacerbate AD development by enhancing inflammation.

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