Diagnostic performance of salivary markers of Alzheimer's disease: A systematic review

Abstract High heterogeneity of diagnostic accuracy have been reported for salivary markers of Alzheimer's disease (AD), but the reasons remain unclear. This systematic review aims to evaluate the potential sources of heterogeneity in the diagnostic performance of salivary biomarkers for the identification of AD. We systematically reviewed four databases for studies from inception to 2025. We evaluated biomarker sensitivity, specificity, and area under the curve (AUC). This study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) statement. Of 3118 studies, 18 met the inclusion criteria. AUC data were available only for amyloid beta (Aβ)42 and lactoferrin. Pre‐analytical properties were a major source of heterogeneity, comprehending prior orientation, time of collection, recipient material, and centrifugation methods. The main source of variability likely stems from substantial differences in pre‐analytical procedures across studies. Further studies on salivary biomarkers in AD implementing standardized protocols are warranted.