Non-invasive optical detection of salivary Aβ in mouse models of Alzheimer’s disease

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases, particularly prevalent in the aging population. While therapeutic interventions are most effective during the early stages, there remains a critical need for cost-effective and broadly accessible tools for early diagnosis and large-scale screening. Here, we present a novel approach to measure amyloid-β proteins as biomarkers of AD in the saliva of 5xFAD and hAPPsl mouse models, with an ultrasensitive point of care platform. Combining Total Internal Reflection Scattering (TIRS) microscopy with antibody-functionalized metallic nanoparticles (NPs), our platform allows for the quantification of Aβ42 and Aβ40 in AD mouse models saliva and discriminates transgenic and wild type animals with an accuracy of 90.5% and an average specificity of 87.5%. Additionally, we demonstrate the correlation of Aβ concentration in the saliva with the Aβ content in hippocampus and cortex showing a direct link between biomarker and pathology in the brain.