The eye as a window to the brain: hyperspectral retinal imaging as a biomarker for Alzheimer’s disease

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is a neurodegenerative disorder that is the leading cause of dementia, affecting more than 50 million people worldwide. In the search for new biomarkers, increasing attention has been dedicated to the retina. As part of the central nervous system, the retina manifests many of the characteristic pathological processes that occur in the AD brain. Moreover, it can be imaged at low‐cost and non‐invasively at high resolution, and therefore it may be used for AD diagnosis and monitoring. In this context, emerging evidence suggests the potential of in vivo hyperspectral retinal imaging (HSRI) as a potential biomarker for brain amyloid‐β accumulation. Therefore, this project aims at studying HSRI as a novel biomarker that could lead to inexpensive population screening, thereby removing one of the principal bottlenecks to therapeutic advances in AD.MethodIn this study, we seek to define the molecular basis, sensitivity, and specificity of the HSRI signal of AD, and whether it can distinguish AD from other dementias in a translational pre‐clinical and clinical research project. We perform HSRI of synthetic protein aggregates, and different cell and mouse models of neurodegenerative proteinopathies, and correlate these data with molecular biology assays, to study the molecular basis and pathological correlates of HSRI signals. In a parallel clinical study, we assess the correlation between amyloid status and HSRI and evaluate whether the diagnostic power of HSRI can be increased via a multimodal imaging approach.ResultOur preliminary results demonstrate that HSRI can be used to quantify retinal amyloid in AD animal models and post‐mortem tissues as well as discriminate between AD patients and controls, with improvement in classification accuracy by including optical coherence tomography (OCT) data.ConclusionThis research study covers out‐of‐the‐box thinking to transform the detection of AD. It collects evidence of the specificity and molecular basis of HSRI which is essential for its rational clinical use as an AD imaging biomarker.