Salivary biomarkers for the diagnosis and monitoring of neurological diseases

Abstract

Current research efforts on neurological diseases are focused on identifying novel disease biomarkers to aid in diagnosis, provide accurate prognostic information and monitor disease progression. With advances in detection and quantification methods in genomics, proteomics and metabolomics, saliva has emerged as a good source of samples for detection of disease biomarkers. Obtaining a sample of saliva offers multiple advantages over the currently tested biological fluids as it is a non-invasive, painless and simple procedure that does not require expert training or harbour undesirable side effects for the patients. Here, we review the existing literature on salivary biomarkers and examine their validity in diagnosing and monitoring neurodegenerative and neuropsychiatric disorders such as autism and Alzheimer's, Parkinson's and Huntington's disease. Based on the available research, amyloid beta peptide, tau protein, lactoferrin, alpha-synuclein, DJ-1 protein, chromogranin A, huntingtin protein, DNA methylation disruptions, and micro-RNA profiles provide display a reliable degree of consistency and validity as disease biomarkers.

Keywords: Dementia; Diagnosis; Neurodegeneration; Neurological diseases; Salivary biomarkers.

Fig. 1

The normal and AD pathogenic pathway of APP processing into its multiple derivatives. In a healthy individual the primary processing of APP by α-secretase within the Aβ sequence produces the s-APPα which is released to the extracellular domain. This cleavage of the Aβ domain inactivates its amyloidogenic potential. The cleavage of the produced C-83 peptide by γ-secretase produces the P3 peptide which is released to the extracellular space and the AICD which remains inside the cell. The difference between the normal APP processing pathway and that of AD is the initial cleavage of APP by β-secretase in AD, producing an s-APPβ and conserving the Aβ sequence. Aβ is then released after C-99 processing by γ-secretase. Once secreted to the extracellular space, Aβ is free to aggregate and form amyloid plaques.

Fig. 2

Summary of salivary biomarkers and their current state of validity. This figure classifies the neurological disorders into four different types: neurodevelopmental, cognitive, motor and neuropsychiatric disorders. For each one of these disorders, a categorical system classifies the biomarkers as: promising, inconclusive and negative results based upon the findings of our work. Abbreviations used: AD: Alzheimer's disease; PD: Parkinson's disease; MS: Multiple Sclerosis; ASD: Autism Spectrum Disorder; ALS: Amyotrophic Lateral Sclerosis; HD: Huntington's disease; and NPD: Neuropsychiatric Disorders.