{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:39:12Z","timestamp":1791851952326,"version":"4.3.4"},"reference-count":159,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,6,4]],"date-time":"2023-06-04T00:00:00Z","timestamp":1685836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a neurodegenerative disease and the most common example of dementia. The neuropathological features of AD are the abnormal deposition of extracellular amyloid-\u03b2 (A\u03b2) and intraneuronal neurofibrillary tangles with hyperphosphorylated tau protein. It is recognized that AD starts in the frontal cerebral cortex, and then it progresses to the entorhinal cortex, the hippocampus, and the rest of the brain. However, some studies on animals suggest that AD could also progress in the reverse order starting from the midbrain and then spreading to the frontal cortex. Spirochetes are neurotrophic: From a peripheral route of infection, they can reach the brain via the midbrain. Their direct and indirect effect via the interaction of their virulence factors and the microglia potentially leads to the host peripheral nerve, the midbrain (especially the locus coeruleus), and cortical damage. On this basis, this review aims to discuss the hypothesis of the ability of Treponema denticola to damage the peripheral axons in the periodontal ligament, to evade the complemental pathway and microglial immune response, to determine the cytoskeletal impairment and therefore causing the axonal transport disruption, an altered mitochondrial migration and the consequent neuronal apoptosis. Further insights about the central neurodegeneration mechanism and Treponema denticola\u2019s resistance to the immune response when aggregated in biofilm and its quorum sensing are suggested as a pathogenetic model for the advanced stages of AD.<\/jats:p>","DOI":"10.3390\/ijerph20116049","type":"journal-article","created":{"date-parts":[[2023,6,5]],"date-time":"2023-06-05T02:57:47Z","timestamp":1685933867000},"page":"6049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Treponema denticola Has the Potential to Cause Neurodegeneration in the Midbrain via the Periodontal Route of Infection\u2014Narrative Review"],"prefix":"10.3390","volume":"20","author":[{"given":"Flavio","family":"Pisani","sequence":"first","affiliation":[{"name":"Faculty of Clinical and Biomedical Sciences, School of Dentistry, University of Central Lancashire, Preston PR1 2HE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Pisani","sequence":"additional","affiliation":[{"name":"IRCCS, \u201cSanta Lucia\u201d Foundation, Neurology and Neurorehabilitation Unit, Via Ardeatina, 306, 00179 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Arcangeli","sequence":"additional","affiliation":[{"name":"Azienda Sanitaria Locale ASLRM1, Nuovo Regina Margherita Hospital, Geriatric Department, Advanced Centre for Dementia and Cognitive Disorders, Via Emilio Morosini, 30, 00153 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Harding","sequence":"additional","affiliation":[{"name":"Dementia and Neurodegenerative Disease Research Group, Faculty of Clinical and Biomedical Sciences, School of Dentistry, University of Central Lancashire, Preston PR1 2HE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simarjit","family":"Singhrao","sequence":"additional","affiliation":[{"name":"Dementia and Neurodegenerative Disease Research Group, Faculty of Clinical and Biomedical Sciences, School of Dentistry, University of Central Lancashire, Preston PR1 2HE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/prd.12452","article-title":"Mental health and periodontal and peri-implant diseases","volume":"90","author":"Ball","year":"2000","journal-title":"Periodontology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00784-017-2264-2","article-title":"Oral hygiene and oral health in older people with dementia: A comprehensive review with focus on oral soft tissues","volume":"22","author":"Delwel","year":"2018","journal-title":"Clin. 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