Treponema denticola Has the Potential to Cause Neurodegeneration in the Midbrain via the Periodontal Route of Infection—Narrative Review

Abstract

Alzheimer’s 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-β (Aβ) 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’s 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.

Influence of HIV infection on cognition and overall intelligence in HIV-infected individuals: advances and perspectives

“…We are of the opinion that HIV positive individuals having the preceding attributes are potentially likely to display lower IQ scores. Our opinion is further supported by the observations of some authors who have shown that oral colonization with microorganisms such as Treponema denticola, is associated with cognitive impairment (Pisani et al, 2022;Tang et al, 2022;Pisani et al, 2023). In a context of HIV infection, and when considering C. albicans as the microorganism of interest, the preceding outcome is potentially also likely.…”