Because the neurodegenerative processes in Alzheimer’s disease (AD) develop over a prolonged time that can span decades, there is a critical need to identify individuals during this preclinical period when potential interventions might be more effective.  While current diagnostic tools, such as neuroimaging and CSF sampling, continue to aid in preclinical detection of AD, they are expensive and/or invasive, thereby limiting their clinical utility as biomarkers. In this study, we will explore the use of saliva as an alternative biofluid for biomarker research. One of the main advantages of saliva as a biofluid is that it is easy to collect in a non-invasive way, hence, can reduce discomfort and anxiety for the patient, especially in elderly populations. Further, compared to blood sampling, whole saliva collection requires no specially trained personnel and does not need to be processed immediately allowing for sample collection in any setting. In the current application, we will investigate salivary levels of neuronal (neurofilament light) and glial (YKL-40) biomarkers to assess their potential to represent indicators of early cognitive decline.  Salivary biomarkers, such as those investigated in this proposal, possibly in combination with conventional diagnostic clues such as genotype and amyloid burden, may provide robust stratification and selection of early-stage patients who are most suitable for early interventions.