top of page

[AWC 3rd Place] Rewriting Destiny: Genetic Engineering's Potential in P. gingivalis-Associated AD

1.0 Introduction

Genetic engineering, a cutting-edge field of biotechnology, has opened up new frontiers in medical research and treatment (Komor et al., 2016; Shin et al., 2017; Lee et al., 2019). One of the most intriguing areas of study is the potential link between genetic engineering and Alzheimer's Disease (AD), a neurodegenerative disorder characterized by cognitive decline and memory loss (Bahar et al., 2021). Emerging research has unveiled a connection between the oral pathogen Porphyromonas gingivalis (P. gingivalis) and AD (Dominy et al., 2019). As the scientific community peers into this uncharted territory, an enthralling narrative emerges at the juncture of genetic engineering, P. gingivalis, and AD, hinting at the transformative potential of genetic manipulation in deepening our comprehension and redefining our approach to combatting this complex malady. This article delves into the intersection of genetic engineering, P. gingivalis, and AD, shedding light on the potential for genetic manipulation to revolutionize our understanding and management of this debilitating disease.


1.1 P gingivalis & AD

AD, an intricate mosaic of neuronal dysfunction, has long posed one of the most profound challenges in modern medicine (Association, 2019). Characterized by the insidious degradation of cognitive abilities, memory loss, and emotional upheavals, AD imposes an immense burden on patients, caregivers, and healthcare systems worldwide (Atri, 2019). Yet, as researchers strive to decipher its underlying mechanisms, they have encountered a compelling clue – an unexpected and intricate web of interactions between AD and an entity far removed from the cerebral realm: Porphyromonas gingivalis.


Traditionally known as an oral pathogen, P. gingivalis's association with AD has ignited a paradigm shift in how we perceive the intricate interplay between oral health and cognitive well-being (Bostanci and Belibasakis, 2012). Emerging studies have illuminated a link between chronic periodontal infections, often instigated by P. gingivalis, and a heightened susceptibility to AD. This connection appears to stem from a cascade of events wherein P. gingivalis, originating in the oral cavity, disseminates and potentially triggers neuroinflammation and the accumulation of amyloid beta plaques in the brain – hallmark features of AD pathology (Dominy et al., 2019; Patel et al., 2021).


In the midst of this scientific intrigue, genetic engineering emerges as a formidable vanguard, poised to reshape our understanding of this intricate web of connections. This innovative discipline enables scientists to not merely observe from a distance but to actively delve into the genetic codes that govern both P. gingivalis and AD. Through precise manipulation of genetic material, scientists can craft bespoke models that mirror the interactions between the pathogen and the brain, illuminating pathways, interactions, and potential causal relationships.



2.0 Genetic Engineering: A Tool for Precision Investigation and Treatment

Genetic engineering offers a powerful toolset to explore the complex relationship between P. gingivalis and AD. With techniques like CRISPR-Cas9, scientists can engineer animal models that mimic the interactions between the bacteria and the brain, allowing for a more detailed understanding of the mechanisms at play (Shin et al., 2017). Moreover, genetic manipulation enables researchers to modify specific genes associated with both P. gingivalis infection and AD pathology, offering insights into causality and potential therapeutic targets (Visanji et al., 2015).


For example:

  • Creating Animal Models to Mimic P. gingivalis Interactions

Genetic engineering allows scientists to engineer animal models that closely mimic the interactions between P. gingivalis and the brain. By introducing specific genetic modifications to replicate the inflammatory response seen in chronic periodontal infections, researchers can observe the progression of AD-like pathology and gain insights into the causal relationship between P. gingivalis and AD. These models help identify key molecular players and pathways, aiding in the development of targeted therapies. Similar study done Phillips et al., has shown promising outcomes for cell transplantation using these modifications (Phillips and Tang, 2008).


  • Gene Editing to Unravel Mechanisms

CRISPR-Cas9 technology has enabled scientists to edit specific genes involved in P. gingivalis infection and AD pathology. For example, researchers can manipulate genes responsible for amyloid beta production or immune response regulation. By observing the effects of these genetic modifications, scientists gain a deeper understanding of how P. gingivalis contributes to amyloid plaque formation and neuroinflammation, shedding light on potential therapeutic targets.


  • Exploring Genetic Susceptibility

Genetic engineering allows researchers to identify and manipulate genes associated with susceptibility to both P. gingivalis infection and AD. By studying individuals with genetic predispositions to periodontal diseases and AD, scientists can pinpoint shared genetic factors that contribute to susceptibility. For instance, variations in immune response genes might influence the likelihood of developing both conditions. Such insights guide the development of personalized preventive strategies and therapies tailored to an individual's genetic makeup.


  • Editing Immune Response Genes:

In a breakthrough study, researchers used CRISPR-Cas9 to modify immune response genes in a mouse model susceptible to P. gingivalis infection (Solbiati et al., 2020). By enhancing the mice's immune system to better combat the pathogen, they observed a significant reduction in both oral bacterial load and brain inflammation. This success demonstrates the potential of genetic engineering to strengthen the body's defenses against P. gingivalis, potentially slowing the progression of AD.


  • Alleviating Neuroinflammation:

Genetic engineering holds promise for designing therapies that target neuroinflammation triggered by P. gingivalis. By manipulating genes responsible for regulating immune responses in the brain, scientists can potentially develop treatments that suppress excessive inflammation while preserving essential immune functions. This approach has the potential to mitigate the neurodegenerative effects of chronic infections and contribute to AD management.


  • Reducing Amyloid Beta Accumulation:

In another notable study, researchers used gene editing techniques to modify genes associated with amyloid beta production in a mouse model (Lu et al., 2021). By reducing the expression of these genes, they observed a decrease in amyloid beta plaque accumulation in the brain. This success exemplifies how genetic engineering can directly impact AD pathology by altering the molecular processes that lead to plaque formation.



3.0 Exploring Genetic Susceptibility

In the intricate tapestry of human health, genetics plays a fundamental role in determining susceptibility to various diseases (The genetic basis of disease - PMC, no date). Among the intriguing frontiers of research lies the exploration of genetic susceptibility to both P. gingivalis infection and AD. By delving into the genetic makeup of individuals who are predisposed to these conditions, scientists aim to unearth the hidden threads that connect these seemingly distinct entities. This quest for genetic susceptibility not only enhances our understanding of disease mechanisms but also holds the potential to revolutionize preventive strategies and therapeutic interventions.


  • Unraveling the Genetic Blueprint of P. gingivalis-Associated AD

In the intricate tapestry of human health, genetics plays a fundamental role in determining susceptibility to various diseases. Among the intriguing frontiers of research lies the exploration of genetic susceptibility to both P. gingivalis infection and AD. By delving into the genetic makeup of individuals who are predisposed to these conditions, scientists aim to unearth the hidden threads that connect these seemingly distinct entities. This quest for genetic susceptibility not only enhances our understanding of disease mechanisms but also holds the potential to revolutionize preventive strategies and therapeutic interventions.


In our very own discovery using bioinformatics we have discovered the common genes associated with P gingivalis and AD, paving the early stages of a genetic predisposition to Pg-AD association (Figure 1) (Hamarsha et al., 2023).


Figure 1 Common genes identified through GEO and bioinformatic tools in our study (Hamarsha et al., 2023).