Tears as a window to Alzheimer's disease: A systematic review of biomarkers for early detection

Alzheimer's disease (AD) is the leading cause of dementia, characterized by the accumulation of amyloid beta and tau proteins, leading to neuronal degeneration and brain atrophy. While cerebrospinal fluid and blood biomarkers have advanced early AD diagnosis, these methods are invasive and costly. This systematic review investigates tears as a non-invasive, accessible source of AD biomarkers. Using tears, directly linked to the central nervous system, we can effectively detect proteins, microRNA (miRNA), and extracellular vesicles (EVs), reflecting neurodegenerative processes. Tear collection is cost effective and minimally stressful, allowing continuous biomarker monitoring across disease stages. This review highlights recent findings on specific proteins, miRNA, and EVs in tears of patients with AD, and examines tear collection and analysis methods. The potential of these techniques for early, accessible disease detection is emphasized. Further research is needed to standardize methods and validate biomarkers in larger cohorts, positioning tears as a valuable tool for early AD diagnosis and management.