Title : Saliva-based testing in Alzheimer’s disease: How do our findings compare with existing evidence?
Abstract:
Background: The demand for practical and minimally invasive biomarkers for Alzheimer’s disease (AD) has increased substantially, particularly in view of the logistical, economic, and acceptability constraints associated with cerebrospinal fluid and blood-based testing. Saliva has gained attention as an alternative biological matrix capable of reflecting neurodegenerative, inflammatory, and neuropsychiatric processes. Nevertheless, existing studies on salivary biomarkers in AD are highly variable with respect to target analytes, laboratory techniques, and clinical populations. Moreover, systematic comparisons between independent cohorts and previously published data remain limited, restricting the translational interpretation of findings. The present study sought to contrast results from an original salivary biomarker cohort with those reported in the literature, focusing on areas of agreement, inconsistency, and methodological influence.
Methods: We conducted an observational investigation including cognitively unimpaired individuals, participants with mild cognitive impairment, and patients with clinically established Alzheimer’s disease. Saliva samples were obtained following standardized collection protocols and analyzed for selected markers of neurodegeneration and inflammation using immunoassay-based methods. In parallel, a structured narrative comparison of published human studies evaluating salivary biomarkers in AD was undertaken. Studies were selected according to predefined criteria, including confirmed clinical diagnosis, use of saliva as the biological substrate, and quantitative biomarker measurement. Data on biomarkers, analytical platforms, cohort characteristics, and reported outcomes were systematically reviewed and qualitatively compared with findings from our cohort.
Results: Distinct salivary biomarker patterns were observed across cognitive stages in our cohort, with trajectories consistent with progressive neurodegeneration. Comparison with previously published studies revealed partial alignment for specific biomarkers, particularly those associated with tau-related pathology and inflammatory pathways. However, substantial variability across studies was evident, largely driven by differences in analytical sensitivity, saliva collection and processing procedures, and clinical heterogeneity of study populations. Several biomarkers described as promising in individual reports demonstrated limited reproducibility across independent investigations, highlighting the impact of methodological diversity.
Conclusion: These results reinforce the biological relevance of saliva as a source of biomarkers for Alzheimer’s disease while emphasizing the challenges posed by lack of standardization and inter-study comparability. The comparative framework applied in this study supports the role of salivary biomarkers as a complementary diagnostic approach and underscores the need for methodological harmonization and multicenter validation. Saliva-based testing represents a promising avenue for scalable screening and research, particularly in contexts where invasive procedures are impractical or inaccessible.
