Imaging of Neurovascular Response for Assessment of Alzheimer's Disease

ABSTRACT Alzheimer’s disease (AD) is the most common cause of dementia and currently the seventh leading cause of deaths in the United States. In the absence of any therapeutics that can undo neurological damage associated with AD, it is well established that early detection of AD can lead to improved outcomes for the patient, the care provider, and the payor. Our project seeks to pursue a bold avenue for an early-stage biomarker for AD by enabling rapid, noninvasive assessment of cerebrovascular dysfunction, which is known to be impaired in AD. Because assessment of localized neurovascular reactivity (NVR) in the brain is difficult to accomplish noninvasively, we seek to estimate it using observations in the retina and retinal vasculature which are known to share structural and functional similarities with the brain. During Phase I, we will demonstrate proof of concept in animal models. Our proposed solution – VasoVUE NV – will stimulate the mouse retina with flicker illumination and use laser speckle contrast imaging (LSCI) to monitor concomitant blood flow changes. Observations will be compared with whisker stimulation derived changes in blood flow over the whisker barrel cortex monitored using LSCI and multiphoton microscopy. Once validated, stimulus-evoked blood flow response will be obtained from the retinae and cortical regions of transgenic mice demonstrating amyloid pathology and compared with controls to assess the feasibility of detecting NVR impairment. In doing so, we will develop an in vivo imaging platform (VasoVUE Lab) that can be marketed to academic researchers for simultaneous, synchronous stimulation and imaging of the eye and brain and find broad use in oculomics investigations on AD and other neurodegenerative diseases. If our Phase I project is successful, we expect to develop a clinical-grade instrument for retina-based NVR assessment and conduct clinical validation during Phase II studies.