Biomarkers help in the diagnosis and evaluation of therapies. They can be measured relatively easily in blood, cerebrospinal fluid (CSF), urine or saliva. The omics methods available today (genomics, RNomics, proteomics and metabolomics) enable the rapid detection of thousands of markers, even in small volumes. Saliva is readily available and therefore lends itself to the early diagnosis of neurodegenerative diseases. In today's blog post, I would like to present a review paper by Christine Zürcher and Christian Humpel from Innsbruck, which was published in December 2023.
A wide variety of substances can be exchanged between saliva and the human brain by means of the mouth-brain axis: via the cranial nerves or the airway through the nose, but also via the lymphatic pathway or the peripheral bloodstream. It has long been known that saliva can be useful not only for the detection of oral and systemic diseases, but also for brain diseases, in particular through the detection of antibodies and inflammatory proteins (matrix metalloproteinases, interleukins or tumor necrosis factor TNF). Elevated levels of alpha-2-macroglobulin in saliva, for example, indicate the glycemic situation in type 2 diabetes mellitus.
Alzheimer's disease is characterized by Aβ deposits (extracellular plaques) and tau pathology (hyperphosphorylated tau causes neurofibrillary tangles). As discussed in my book on neurodegeneration, research is being conducted on laboratory diagnosis using CSF, as the determination of Aβ-42 and -40, total tau and phospho-tau-181 can distinguish Alzheimer's patients from healthy individuals with high specificity and sensitivity. Unfortunately, these biomarkers are limited by the invasive measures used to obtain cerebrospinal fluid. For this reason, more easily accessible human fluids such as blood, urine or saliva are currently being intensively investigated.
A simple laboratory test for Alzheimer's disease by measuring acetylcholinesterase in saliva was presented back in 2008 and more recent studies suggest that Aβ42 could also be a potential biomarker. In addition, total tau and phospho-tau-181 can now be reliably determined in saliva. Human saliva therefore not only supports the diagnosis of oral diseases, cancer or diabetes, but also contributes to the detection of neurodegenerative diseases. Spitting directly into a tube appears to be the optimal method of collection and allows diagnosis within a few hours. However, as an alternative to invasive sampling after lumbar or venipuncture, the procedure for collecting and analyzing saliva still needs to be validated. The measured values often exhibit a high degree of variability, as the composition of saliva is also influenced by exogenous factors.
Reference:
Zürcher C, Humpel C (2023) Saliva: a challenging human fluid to diagnose brain disorders with a focus on Alzheimer's disease. Neural Regen Res 18:2606
Image credit: iStock/burco onter