Salivaomics: New Frontiers in Studying the Relationship Between Periodontal Disease and Alzheimer’s Disease
Giuseppina Malcangi, Grazia Marinelli, Alessio Danilo Inchingolo, Irma Trilli, Laura Ferrante, Lucia Casamassima, Paola Nardelli, Francesco Inchingolo, Andrea Palermo, Angelo Michele Inchingolo, Gianna Dipalma
Abstract
BACKGROUND: This study explores the link between oral biofluids, microbial dysbiosis, and Alzheimer's disease (AD), highlighting saliva and gingival crevicular fluid (GCF) as non-invasive diagnostic sources. AD onset and progression appear to be influenced not only by genetic and environmental factors but also by changes in the oral microbiome and related inflammatory and metabolic alterations. As global populations age, the incidence of AD is projected to rise significantly. Emerging evidence implicates the oral microbiome and salivary metabolites in neurodegenerative pathways, suggesting that oral health may mirror or influence brain pathology. MATERIALS AND METHODS: A systematic review of recent multi-omics studies was performed, focusing on salivary and GCF analysis in patients with AD, those with mild cognitive impairment (MCI), and cognitively healthy individuals. Databases searched included PubMed, Web of Science, and Scopus, following PRISMA guidelines. RESULTS: Across the 11 included studies, significant alterations were reported in both the salivary microbiome and metabolome in AD patients. Notable microbial shifts involved increased abundance of Veillonella parvula and Porphyromonas gingivalis, while key metabolites such as L-tyrosine, galactinol, and mannitol were consistently dysregulated. These biomarkers correlated with cognitive performance and systemic inflammation. CONCLUSIONS: Oral biofluids represent promising, accessible sources of biomarkers for early AD detection. Multi-omics integration reveals the oral-brain axis as a potential target for diagnosis, monitoring, and therapeutic strategies.