Saliva acts as an accessible biological fluid rich in biochemical, molecular, and protein compounds that are transferred into this environment through blood–salivary barriers and the autonomic nervous system, making it a non‑invasive “biological mirror” for monitoring the central nervous system and a substitute for cerebrospinal fluid (CSF). In this review article, by searching PubMed, Google Scholar, Scopus, and ScienceDirect, 77 articles out of 89 studies published between 2015 and 2025 were selected based on keywords. The studies showed that specific neural proteins such as α‑synuclein, β‑amyloid, tau, huntingtin, and MBP; metabolites; cytokines (TNF‑α, IL‑6); neurotransmitters; and salivary small RNAs accurately reflect the pathological changes of neurodegeneration, inflammation, and stress in diseases such as Parkinson’s, Alzheimer’s, ischemic stroke, Huntington’s disease, multiple sclerosis (MS), and anxiety/stress disorders. Biomarkers such as α‑synuclein oligomers in Parkinson’s, Aβ42/p‑tau in Alzheimer’s, inflammatory cytokines in stroke, mHTT/BDNF in Huntington’s, IgA/FLC/sHLA‑II in MS, and cortisol/α‑amylase in psychiatric disorders show significant correlations with CSF levels or clinical indices and provide high‑accuracy (AUC > 0.85) preclinical detection, monitoring of disease progression, and differential diagnosis, while salivary miRNAs ensure stability and regulatory roles in neuronal survival. Salivary diagnostics, empowered by Omics, nano, and AI technologies, enables large‑scale screening, therapeutic monitoring, and early detection, laying the foundation for precise, cost‑effective, and practical diagnostic methods in the future of personalized medicine. |
