PROJECT SUMMARY / ABSTRACT Alzheimer's disease (AD) is the most widespread neurodegenerative disorder. Despite the severity of the disease, early diagnosis of AD is still challenging due to the low accuracy or high cost of neuropsychological tests and neuroimaging. Development of an accurate and cost-effective technology for non-invasive screening and monitoring of AD before irreversible brain damage or mental decline is critical. WellSIM proposes to develop and validate a highly sensitive immunofluorescence assay, termed EXODOTS, for detection and quantification of AD core biomarkers from circulating extracellular vesicles (EV) with high accuracy, high speed, and low cost. This blood-based assay will facilitate minimally invasive assessment of AD patients in primary care settings and continuous monitoring of disease progression.