Guidelines for the standardization of pre‐analytical variables for salivary biomarker studies in Alzheimer's disease research: An updated review and consensus of the Salivary Biomarkers for Dementia Research Working Group

There is a pressing need for accessible biomarkers with high diagnostic accuracy for Alzheimer's disease (AD) diagnosis to facilitate widespread screening, particularly in underserved groups. Saliva is an emerging specimen for measuring AD biomarkers, with distinct contexts of use that could complement blood and cerebrospinal fluid and detect various analytes. An interdisciplinary, international group of AD and related dementias (ADRD) researchers convened and performed a narrative review of published studies on salivary AD biomarkers. We critically appraised the current state of the literature, examining both consistencies and discrepancies in existing pre-analytical variables and methodologies. We discussed how various pre-analytical variables could influence the detection and quantification of salivary biomarkers, showed technologies available to standardize collection procedures, and proposed a standardized pre-analytical protocol to guide future studies on salivary AD biomarker examinations. We identified potential contexts of use, gaps, and priorities and proposed future research directions. HIGHLIGHTS: Given its non-invasive nature, wider accessibility, and cultural acceptability, particularly in low-resourced settings, saliva is a biofluid complementary to blood and CSF. Current salivary AD biomarker studies do not control for many confounding pre-analytical variables during the sampling process, potentially leading to inaccurate salivary biomarker readings and conclusions, contributing to conflicting findings. Reviewing the current literature, including the consistencies and non-consistencies observed in the existing parameters and methodologies, discussing how they can affect salivary AD biomarker detection and quantification. Proposing a standardized salivary pre-analytical protocol, identifying the gaps and prioritizations needed to move this area forward, proposing future directions and potential contexts of use.