Alziemer's Disease and Periodontal Disease Bidirectional Interrelationships

Ramya, V.; Bhuvaneshwarri,; Paddmanabhan, Preethe; Manisundar, N.

doi:10.13005/bbra/1264

Cited by 5 publications

(4 citation statements)

References 6 publications

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“…As a peripheral chronic infection, periodontitis can trigger the onset of proinflammatory signaling cascades, weakening the blood-brain barrier (BBB) and resulting in direct CNS colonization by bacteria 46,60,61 . Moreover, the neurotropism of spirochetal www.nature.com/scientificreports www.nature.com/scientificreports/ periopathogens enables their spread through cranial nerves and propagation along the olfactory and trigeminal tracts 23,24,62 . The present study has found that the DNA of P. gingivalis, a causative agent of chronic periodontitis that has recently been isolated from the brain of people afflicted with AD 63 and is believed to be involved in the disease pathogenesis, triggers Tau misfolding.…”

Section: Discussionmentioning

confidence: 99%

Bacterial DNA promotes Tau aggregation

Tetz

Pinho²,

Pritzkow³

et al. 2020

Sci Rep

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A hallmark feature of Alzheimer's disease (AD) and other tauopathies is the misfolding, aggregation and cerebral accumulation of tau deposits. Compelling evidence indicates that misfolded tau aggregates are neurotoxic, producing synaptic loss and neuronal damage. Misfolded tau aggregates are able to spread the pathology from cell-to-cell by a prion like seeding mechanism. The factors implicated in the initiation and progression of tau misfolding and aggregation are largely unclear. In this study, we evaluated the effect of DNA extracted from diverse prokaryotic and eukaryotic cells in tau misfolding and aggregation. Our results show that DNA from various, unrelated gram-positive and gram-negative bacteria results in a more pronounced tau misfolding compared to eukaryotic DNA. Interestingly, a higher effect in promoting tau aggregation was observed for DNA extracted from certain bacterial species previously detected in the brain, CSF or oral cavity of patients with AD. Our findings indicate that microbial DNA may play a previously overlooked role in the propagation of tau protein misfolding and AD pathogenesis, providing a new conceptual framework that positions the compromised blood-brain and intestinal barriers as important sources of microbial DNA in the CNS, opening novel opportunities for therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Bacterial DNA promotes Tau aggregation

Tetz

Pinho²,

Pritzkow³

et al. 2020

Sci Rep

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“…[198][199][200] Microglia very efficiently get rid of invaders and detect synaptic anomalies as they are always patrolling the brain. 194,201,202 At the same time, they are maintained in a quiescent state by their interaction with neurons via CXCR1 203 or CD200L. 204 When activated through different pathways including the TREM2-DAP12, 196,200,205 they can phagocytose and kill intracellularly all types of microorganisms.…”

Section: Cellular Defensementioning

confidence: 99%

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Fülöp¹,

Tripathi²,

Rodrigues³

et al. 2021

NDT

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Alzheimer’s disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of amyloid-beta (Aβ) and its aggregation into amyloid plaques, was accepted for a long time as the main cause of AD. However, many studies showed that Aβ is a frequent consequence of many challenges/pathologic processes occurring in the brain for decades. A key factor, sustained by experimental data, is that low-grade infection leading to production and deposition of Aβ, which has antimicrobial activity, precedes the development of clinically apparent AD. This infection is chronic, low grade, largely clinically silent for decades because of a nearly efficient antimicrobial immune response in the brain. A chronic inflammatory state is induced that results in neurodegeneration. Interventions that appear to prevent, retard or mitigate the development of AD also appear to modify the disease. In this review, we conceptualize further that the changes in the brain antimicrobial immune response during aging and especially in AD sufferers serve as a foundation that could lead to improved treatment strategies for preventing or decreasing the progression of AD in a disease-modifying treatment.

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“…As a peripheral chronic infection, periodontitis can trigger the onset of proinflammatory signaling cascades, weakening the blood-brain barrier (BBB) and resulting in direct CNS colonization by bacteria [46, 57, 58]. Moreover, the neurotropism of spirochetal periopathogens enables their spread through cranial nerves and propagation along the olfactory and trigeminal tracts [23, 24, 59]. The present study has found that the DNA of P.gingivalis , a causative agent of chronic periodontitis that has recently been isolated from the brain of people afflicted with AD [60] and is believed to be involved in the disease pathogenesis, triggers Tau misfolding.…”

Section: Discussionmentioning

confidence: 99%

Bacterial DNA promotes Tau aggregation

Tetz¹,

Pinho²,

Soto³

et al. 2019

Preprint

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A hallmark feature of Alzheimer’s disease (AD) and other tauopathies is the misfolding, aggregation and cerebral accumulation of tau deposits. Compelling evidence indicates that misfolded tau aggregates are neurotoxic, producing synaptic loss and neuronal damage. Misfolded tau aggregates are able to spread the pathology from cell-to-cell by a prion like seeding mechanism. The factors implicated in the initiation and progression of tau misfolding and aggregation are largely unclear. In this study, we evaluated the effect of DNA extracted from diverse prokaryotic and eukaryotic cells in tau misfolding and aggregation. Our results show that DNA from various, unrelated gram-positive and gram-negative bacteria results in a more pronounced tau misfolding compared to eukaryotic DNA. Interestingly, a higher effect in promoting tau aggregation was observed for DNA extracted from certain bacterial species previously detected in the brain, CSF or oral cavity of patients with AD. Our findings indicate that microbial DNA may play a previously overlooked role in the propagation of tau protein misfolding and AD pathogenesis, providing a new conceptual framework that positions the compromised blood-brain and intestinal barriers as important sources of microbial DNA in the CNS, opening novel opportunities for therapeutic interventions.

show abstract

Alziemer's Disease and Periodontal Disease Bidirectional Interrelationships

Cited by 5 publications

References 6 publications

Bacterial DNA promotes Tau aggregation

Bacterial DNA promotes Tau aggregation

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Bacterial DNA promotes Tau aggregation

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