CX3CL1 Delta Chemokine Is a Chronic Inflammatory Mediator That Links Periodontitis with Alzheimers Disease in Patients

Abstract

Titanium is considered a biocompatible biomaterial of dental titanium alloys (Ti-6Al-4V). However, in patients with certain dental metals (Hg++, Al, Ti, etc.), including dental Ti implants, a chronic silent inflammatory state can be provoked. On the other hand, periodontitis favors the adherence of biofilms on the surface of teeth, increasing the local recruitment of innate immune cells (neutrophils, macrophages, anddendritic cells). Thus, a chronic proinflammatory cytokine release of cytokine/chemokines, including CX3CL1, can amplify the local inflammatory responses and also promote oral dysbiosis. In fact, recent studies link Alzheimer’s disease (AD) with periodontitis. However, systemic CX3CL1 andMCP-1 elevations can be also detected in patients with long-termdental Ti implants without periodontitis. Periodontitis favors tooth destruction and also enhances the accumulation of oral biofilm. In fact, porphyromonas gingivalis has been associated with AD, and high systemic CX3CL1 levels have been found to contribute to p-Tau accumulation in the brain of AD transgenic mice.

Thus, this CX3CR1 overexpression as a chronic silent proinflammatory response can predispose patients with periodontal disease and poor buccal hygiene to AD. Collectively, CX3CR1 overproduction affects the normal control of the innate immune system and favors the destruction of the supporting tissues of the teeth in patients with periodontal disease. Thus, the link between AD and periodontitis via CX3CL1 opens up a new therapeutic role of delta chemokine blockers against periodontitis and AD pathology.