Alzheimer's disease (AD) is a progressive and multifactorial disease. Many scientific advances have advanced our understanding of the pathogenesis of AD. However, the clinical diagnosis of AD remains difficult, with only post-mortem assays confirming its definitive diagnosis. There is a crucial need for an early and accurate detection of AD related symptoms. To date, current diagnosis techniques are costly or invasive. Finding a peripheral biomarker that could provide a sensitive, reproducible, and accurate detection prior to the onset of the AD clinical symptoms will allow identification of "at risk" individuals, thereby facilitating early initiation of treatments that may prove more effective. Salivary glands contain stem cells, which are affected by aging, suggesting that tissue samples from these glands may reveal a stem cell biomarker of AD, but also stem cells may be harvested from these glands, with proper timing and isolation technique, for cell-based regenerative medicine. Alternatively, instead of the salivary glands, saliva may represent an attractive source for biomarkers due to minimal discomfort to the patient, non-invasive collection, and the possibility of cost-effective screening large populations, encouraging greater compliance in clinical trials and frequent testing. In addition, salivary glands contain stem cells, which are likely also present in the saliva, making these cells as potentially sensitive cellular biomarker of and a therapeutic agent for AD. The aim of this review is to critically analyze the use of saliva for the identification of circulating biological markers to help the diagnosis of early cognitive impairment associated with AD and to generate insights into the potential application of stem cells derived from salivary glands or saliva as therapeutics (i.e., stem cell transplantation) for the disease.
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