Porphyromonas Gingivalis May Seek the Alzheimer’s Disease Brain to Acquire Iron from Its Surplus

Olsen, Ingar

doi:10.3233/adr-200272

Cited by 7 publications

(3 citation statements)

References 90 publications

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“…Regarding the occurrence of PG and gingipain in the central nervous system of AD patients (Dominy et al, 2019), it was recently hypothesized that the increased availability of free iron in AD brains (Smith et al, 2010;Yang et al, 2022) may attract the migration of PG, as PG requires iron for its growth (Olsen, 2021). In this scenario, increased concentrations of LF in the AD brain could be interpreted as a protective mechanism against free iron and, potentially, PG migration.…”

Section: Lactoferrin and Its Influence On Oral Health Pg And The Cent...mentioning

confidence: 99%

The role of microbiome-host interactions in the development of Alzheimer´s disease

Weber

Dilthey

Finzer

2023

Front. Cell. Infect. Microbiol.

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Alzheimer`s disease (AD) is the most prevalent cause of dementia. It is often assumed that AD is caused by an aggregation of extracellular beta-amyloid and intracellular tau-protein, supported by a recent study showing reduced brain amyloid levels and reduced cognitive decline under treatment with a beta-amyloid-binding antibody. Confirmation of the importance of amyloid as a therapeutic target notwithstanding, the underlying causes of beta-amyloid aggregation in the human brain, however, remain to be elucidated. Multiple lines of evidence point towards an important role of infectious agents and/or inflammatory conditions in the etiology of AD. Various microorganisms have been detected in the cerebrospinal fluid and brains of AD-patients and have thus been hypothesized to be linked to the development of AD, including Porphyromonas gingivalis (PG) and Spirochaetes. Intriguingly, these microorganisms are also found in the oral cavity under normal physiological conditions, which is often affected by multiple pathologies like caries or tooth loss in AD patients. Oral cavity pathologies are mostly accompanied by a compositional shift in the community of oral microbiota, mainly affecting commensal microorganisms and referred to as ‘dysbiosis’. Oral dysbiosis seems to be at least partly mediated by key pathogens such as PG, and it is associated with a pro-inflammatory state that promotes the destruction of connective tissue in the mouth, possibly enabling the translocation of pathogenic microbiota from the oral cavity to the nervous system. It has therefore been hypothesized that dysbiosis of the oral microbiome may contribute to the development of AD. In this review, we discuss the infectious hypothesis of AD in the light of the oral microbiome and microbiome-host interactions, which may contribute to or even cause the development of AD. We discuss technical challenges relating to the detection of microorganisms in relevant body fluids and approaches for avoiding false-positives, and introduce the antibacterial protein lactoferrin as a potential link between the dysbiotic microbiome and the host inflammatory reaction.

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Section: Lactoferrin and Its Influence On Oral Health Pg And The Cent...mentioning

confidence: 99%

The role of microbiome-host interactions in the development of Alzheimer´s disease

Weber

Dilthey

Finzer

2023

Front. Cell. Infect. Microbiol.

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“…The connection between intracellular pathogens and neuropsychiatric symptoms has been known for a long time. Malaria, toxoplasmosis, and lately Porphyromonas gingivalis have been associated with psychopathology, while several viruses were linked to neurodegeneration and developmental disabilities ( Henry et al., 2010 ; Lima et al., 2021 ; Olsen, 2021 ; Chemparthy et al., 2021 ). Along these lines, the 1918 influenza pandemic and the more recent H5N1 epidemic were associated with Parkinson’s disease and autism ( Maurizi, 2010 ; Shuid et al., 2021 ).…”

Section: Cell-cell Fusion In Neuropsychiatric Disordersmentioning

confidence: 99%

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Osorio

Sfera

Anton

et al. 2022

Front. Cell. Infect. Microbiol.

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A growing body of epidemiological and research data has associated neurotropic viruses with accelerated brain aging and increased risk of neurodegenerative disorders. Many viruses replicate optimally in senescent cells, as they offer a hospitable microenvironment with persistently elevated cytosolic calcium, abundant intracellular iron, and low interferon type I. As cell-cell fusion is a major driver of cellular senescence, many viruses have developed the ability to promote this phenotype by forming syncytia. Cell-cell fusion is associated with immunosuppression mediated by phosphatidylserine externalization that enable viruses to evade host defenses. In hosts, virus-induced immune dysfunction and premature cellular senescence may predispose to neurodegenerative disorders. This concept is supported by novel studies that found postinfectious cognitive dysfunction in several viral illnesses, including human immunodeficiency virus-1, herpes simplex virus-1, and SARS-CoV-2. Virus-induced pathological syncytia may provide a unified framework for conceptualizing neuronal cell cycle reentry, aneuploidy, somatic mosaicism, viral spreading of pathological Tau and elimination of viable synapses and neurons by neurotoxic astrocytes and microglia. In this narrative review, we take a closer look at cell-cell fusion and vesicular merger in the pathogenesis of neurodegenerative disorders. We present a “decentralized” information processing model that conceptualizes neurodegeneration as a systemic illness, triggered by cytoskeletal pathology. We also discuss strategies for reversing cell-cell fusion, including, TMEM16F inhibitors, calcium channel blockers, senolytics, and tubulin stabilizing agents. Finally, going beyond neurodegeneration, we examine the potential benefit of harnessing fusion as a therapeutic strategy in regenerative medicine.

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“…Untreated, it may end with tooth loss. It is a widely prevalent disease in adults all over the world ( Eke et al, 2016 ) and has in several reports been associated with Alzheimer’s disease (AD) (for a review, see Olsen, 2021 ). Porphyromonas gingivalis , which is considered a keystone bacterium in “chronic” periodontitis ( Socransky et al, 1998 ; Darveau et al, 2012 ; Hajishengallis et al, 2012 ), has been detected in the brains of subjects with AD together with its toxic proteases—gingipains ( Dominy et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Porphyromonas gingivalis-Induced Neuroinflammation in Alzheimer’s Disease

Olsen

2021

Front. Neurosci.

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“Chronic” periodontitis and its keystone pathogen Porphyromonas gingivalis have repeatedly been associated with Alzheimer’s disease (AD). Pathological hallmarks in AD are brain accumulations of amyloid-beta and neurofibrillary tangles consisting of aggregated and hyperphosphorylated tau. In addition, neuroinflammation induced by P. gingivalis has increasingly been recognized as a factor in the pathogenesis of AD. The present mini-review discusses possible mechanisms for the induction of neuroinflammation by P. gingivalis in AD, involving factors such as pro-inflammatory mediators, amyloid-beta, tau, microglia, cathepsin B, and protein kinase R. Inflammagens of P. gingivalis such as lipopolysaccharide and gingipains are also discussed.

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Porphyromonas Gingivalis May Seek the Alzheimer’s Disease Brain to Acquire Iron from Its Surplus

Cited by 7 publications

References 90 publications

The role of microbiome-host interactions in the development of Alzheimer´s disease

The role of microbiome-host interactions in the development of Alzheimer´s disease

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Porphyromonas gingivalis-Induced Neuroinflammation in Alzheimer’s Disease

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