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Review

The Mechanistic Pathways of Periodontal Pathogens Entering the Brain: The Potential Role of Treponema denticola in Tracing Alzheimer’s Disease Pathology

1
School of Dentistry, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK
2
Neurology and Neurorehabilitation Unit, I.R.C.C.S. “Santa Lucia” Foundation, Via Ardeatina, 306-00179 Rome, Italy
3
Azienda Sanitaria Locale ASLRM1, Geriatric Department, Regina Margherita Hospital, Via Emilio Morosini, 30-00153 Rome, Italy
4
Dementia and Neurodegenerative Disease Research Group, Faculty of Clinical and Biomedical Sciences, School of Dentistry, University of Central Lancashire, Preston PR1 2HE, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Paul B. Tchounwou
Int. J. Environ. Res. Public Health 2022, 19(15), 9386; https://doi.org/10.3390/ijerph19159386
Received: 30 June 2022 / Revised: 26 July 2022 / Accepted: 27 July 2022 / Published: 31 July 2022
(This article belongs to the Special Issue Basics of Hygiene in Public Health and Health Promotion)
Alzheimer’s Disease (AD) is a complex neurodegenerative disease and remains the most common form of dementia. The pathological features include amyloid (Aβ) accumulation, neurofibrillary tangles (NFTs), neural and synaptic loss, microglial cell activation, and an increased blood–brain barrier permeability. One longstanding hypothesis suggests that a microbial etiology is key to AD initiation. Among the various periodontal microorganisms, Porphyromonas gingivalis has been considered the keystone agent to potentially correlate with AD, due to its influence on systemic inflammation. P. gingivalis together with Treponema denticola and Tannerella forsythia belong to the red complex consortium of bacteria advocated to sustain periodontitis within a local dysbiosis and a host response alteration. Since the implication of P. gingivalis in the pathogenesis of AD, evidence has emerged of T. denticola clusters in some AD brain tissue sections. This narrative review explored the potential mode of spirochetes entry into the AD brain for tracing pathology. Spirochetes are slow-growing bacteria, which can hide within ganglia for many years. It is this feature in combination with the ability of these bacteria to evade the hosts’ immune responses that may account for a long lag phase between infection and plausible AD disease symptoms. As the locus coeruleus has direct connection between the trigeminal nuclei to periodontal free nerve endings and proprioceptors with the central nervous system, it is plausible that they could initiate AD pathology from this anatomical region. View Full-Text
Keywords: Alzheimer’s disease; periodontal disease; Treponema denticola; Porphyromonas gingivalis; trigeminal nerve; mesencephalic trigeminal nucleus; locus coeruleus Alzheimer’s disease; periodontal disease; Treponema denticola; Porphyromonas gingivalis; trigeminal nerve; mesencephalic trigeminal nucleus; locus coeruleus
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MDPI and ACS Style

Pisani, F.; Pisani, V.; Arcangeli, F.; Harding, A.; Singhrao, S.K. The Mechanistic Pathways of Periodontal Pathogens Entering the Brain: The Potential Role of Treponema denticola in Tracing Alzheimer’s Disease Pathology. Int. J. Environ. Res. Public Health 2022, 19, 9386. https://doi.org/10.3390/ijerph19159386

AMA Style

Pisani F, Pisani V, Arcangeli F, Harding A, Singhrao SK. The Mechanistic Pathways of Periodontal Pathogens Entering the Brain: The Potential Role of Treponema denticola in Tracing Alzheimer’s Disease Pathology. International Journal of Environmental Research and Public Health. 2022; 19(15):9386. https://doi.org/10.3390/ijerph19159386

Chicago/Turabian Style

Pisani, Flavio, Valerio Pisani, Francesca Arcangeli, Alice Harding, and Simarjit Kaur Singhrao. 2022. "The Mechanistic Pathways of Periodontal Pathogens Entering the Brain: The Potential Role of Treponema denticola in Tracing Alzheimer’s Disease Pathology" International Journal of Environmental Research and Public Health 19, no. 15: 9386. https://doi.org/10.3390/ijerph19159386

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