Role of Retinal Amyloid-beta in Neurodegenerative Diseases: Overlapping Mechanisms and Emerging Clinical Applications

Amyloid-beta (A beta) accumulations have been identified in the retina for neurodegeneration-associated disorders like Alzheimer's disease (AD), glaucoma, and age-related macular degeneration (AMD). Elevated retinal A beta levels were associated with progressive retinal neurodegeneration, elevated cerebral A beta accumulation, and increased disease severity with a decline in cognition and vision. Retinal A beta accumulation and its pathological effects were demonstrated to occur prior to irreversible neurodegeneration, which highlights its potential in early disease detection and intervention. Using the retina as a model of the brain, recent studies have focused on characterizing retinal A beta to determine its applicability for population-based screening of AD, which warrants a further understanding of how A beta manifests between these disorders. While current treatments directly targeting A beta accumulations have had limited results, continued exploration of A beta-associated pathological pathways may yield new therapeutic targets for preserving cognition and vision. Here, we provide a review on the role of retinal A beta manifestations in these distinct neurodegeneration-associated disorders. We also discuss the recent applications of retinal A beta for AD screening and current clinical trial outcomes for A beta-associated treatment approaches. Lastly, we explore potential future therapeutic targets based on overlapping mechanisms of pathophysiology in AD, glaucoma, and AMD.