PROJECT SUMMARY The goal of our research is to identify ocular biomarkers that have diagnostic and potentially prognostic utility in Alzheimer's Disease (AD), and establish a relationship to cognition. We seek to determine this relationship in an already established cohort of patients (the Vitreous Biomarkers Study, or VBS) with eye disease where protein biomarkers have been identified in the vitreous humor of the eye and found to be correlated to cognitive function scores on mini-mental status examination (MMSE). There is a need for sensitive and specific diagnostic tests that can detect AD in the early stages. We hypothesize that ocular levels of Aβ and Tau in the aqueous humor of the eye as well as retinal biomarkers of neurodegeneration imaged by Optical Coherence Tomography (OCT), combined with cognitive assessments, may offer a predictive value for detection of early AD. In the VBS, we found that levels of beta amyloid (Aβ40, Aβ42), and total Tau (tTau) in the vitreous humor are correlated with cognitive function scores obtained by mini-mental status examination (MMSE). Drawing from the same patient cohort, we seek to establish the presence of the same proteins in the aqueous humor of the eye (which is more clinically accessible than the vitreous humor), obtain OCT images to look for retinal biomarkers, and repeat MMSE testing to look longitudinally at cognition, and correlate all eye biomarkers with cognition. Additionally, we seek to validate the protein levels in the aqueous and vitreous humor of eyes from postmortem subjects. If a relationship of protein and retinal biomarkers to cognition can be shown, our knowledge of the eye's role in AD will be increased substantially and it will establish the eye as potentially playing a central role in how we diagnose AD.

PROJECT NARRATIVE Investigating the utility of ocular biomarkers and its relationship to cognition, to potentially serve as a tool for early diagnosis, is a novel concept that has not been demonstrated in any prior human or animal studies. If it is found that ocular protein and retinal biomarkers with cognitive assessments play an essential role in diagnosis, it could revolutionize how we diagnose AD. The eye is like a window to the brain and provides unique forms of diagnostic capabilities, and it is our hope that this study will help with actualizing the potential of the eye to show accessible signs of neurological disease, which may help change the way we approach and treat AD.