Exploring the Link Between Periodontitis and Alzheimer's Disease-Could a Nanoparticulate Vaccine Break It?

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, as approximately 55 million people worldwide are affected, with a significant tendency to increase. It reveals three main pathological features: amyloid plaques, neurofibrillary tangles, and neuroinflammation, responsible for the neurodegenerative changes that slowly lead to deterioration of personality and cognitive control. Over a century after the first case report, effective treatments remain elusive, likely due to an incomplete understanding of the precise mechanisms driving its pathogenesis. Recent studies provide growing evidence of an infectious aetiology for AD, a hypothesis reinforced by findings that amyloid beta functions as an antimicrobial peptide. Among the microorganisms already associated with AD, Porphyromonas gingivalis (Pg), the keystone pathogen of periodontitis (PeD), has received particular attention as a possible aetiological agent for AD development. Herein, we review the epidemiological and genetic evidence linking PeD and Pg to AD, highlighting the identification of periodontal bacteria in post mortem analysis of AD patients' brains and identifying putative mechanistic links relevant to the biological plausibility of the association. With the focus on AD research shifting from cure to prevention, the proposed mechanisms linking PeD to AD open the door for unravelling new prophylactic approaches able to reduce the global burden of AD. As hypothesised in this review, these could include a bionanotechnological approach involving the development of an oral nanoparticulate vaccine based on Pg-specific antigens. Such a vaccine could prevent Pg antigens from progressing to the brain and triggering AD pathology, representing a promising step toward innovative and effective AD prevention.