PROJECT SUMMARY The objective of this research is to develop low-cost, non-invasive, electrophysiological biomarkers of brain amyloid and neurodegeneration in patients with Preclinical and Prodromal Alzheimer's disease (AD) using the sleep and resting state electroencephalogram (EEG). Diagnostic criteria recently developed for “Preclinical” and “Prodromal” AD hinge upon measurements of beta-amyloid (Aβ) and changes in brain structure and func- tion. Unfortunately, these “gold standard” biomarkers are too expensive (~$3k/patient), invasive, or specialized for large-scale screening efforts. Thus, there is urgent need for novel cost-effective biomarkers that are rigor- ously linked to established criteria for Preclinical AD. There is a growing appreciation that brain oscillations ob- served in the sleep and resting state EEG are closely associated with underlying AD pathophysiology. It is well known that AD dementia is associated with disrupted sleep dynamics and altered sleep oscillations. Clearance of cerebral Aβ through the brain's glial lymphatic or “glymphatic” system occurs specifically during non-rapid eye movement (NREM) sleep, and is dependent on EEG slow oscillation activity. The cortical generators of sleep and resting state EEG oscillations, which can be estimated using source localization, overlap with brain regions that display cortical thinning and loss of functional connectivity in AD. These relationships have not been extensively studied in preclinical nor prodromal AD. We therefore propose to 1) characterize the rela- tionship between quantitative measures of sleep and resting state EEG and neuroimaging AD bi- omarkers, 2) use these novel relationships alongside known AD-related changes in the EEG to develop EEG-based predictors of AD, and 3) develop a framework for translating these findings into low-cost (as little as $20), highly-scalable tools for screening and tracking of preclinical and prodromal AD.