An Eyedrop Diagnostic Test for Alzheimer's Disease

PROJECT ABSTRACT Alzheimer’s disease (AD) affects 6.9 million people in the U.S. alone and is characterized by the development of amyloid beta plaques, tau neurofibrillary tangles, and neuron loss. This characteristic accumulation of pathological protein aggregates has led to the development of multiple biomarkers for assessing disease status in living individuals, providing them with the opportunity to make informed healthcare decisions and to receive treatment using new FDA-approved drugs that targeting amyloid beta. These biomarkers are also important indicators for measuring the efficacy of therapeutics in clinical trials. The current approach to detect these biomarkers is positron emission tomography (PET) which is sensitive and specific. However, PET is a limited and expensive resource that prevents widespread or frequent biomarker measurements. Other measurements have been developed or are in development, including detection in cerebrospinal fluid and blood, yet these have limitations as well. Tauvision recently identified a fluorescent dye that can label pathological aggregates in the eye and be imaged using standard ophthalmology equipment. Results that suggest our eyedrop-based, non-invasive assay could be a direct measurement of biomarkers in the central nervous system. Our approach represents a highly specific, low-cost measurement that could be used to diagnose and manage AD in a broad population. In this project, we will optimize the structure of the fluorescent compound to improve its specificity and sensitivity for AD in phase 1, with clear metrics for transitioning to phase 2. Then, in phase 2, we will validate our approach in animal models of AD and human tissue from donors with and without AD. This project is a critical first step in translating our potentially breakthrough approach to fill the diagnosis gap in AD.