The Visual System in Alzheimer’s Disease: A Multilevel Review of Pathology, Monitoring, and Intervention

Abstract

Alzheimer’s disease (AD) extends beyond the brain to the visual system, offering a promising window for pathology, monitoring, and intervention. This review synthesizes evidence on AD-related visual impairments across molecular, cellular, circuit, and cortical levels. We examine the eye–brain pathological relationship as a working framework, noting experimental evidence for brain-to-eye amyloid-β (Aβ) transport in mouse models and associations between retinal and cerebral pathology in humans, while emphasizing that bidirectional pathological transport has not been established. Structural and functional changes in the retina, optic nerve, and visual cortex are reviewed, alongside white matter damage and posterior cortical atrophy patterns. We evaluate emerging multimodal tools (OCTA, ERG, and hyperspectral imaging) that shift diagnosis toward an integrated “structure–vessel–function” assessment. We critically examine non-pharmacological interventions, including 40 Hz gamma stimulation and photobiomodulation, discussing their mechanisms, translational challenges, and the dissociation between structural and cognitive outcomes. We propose the visual system as a candidate pathological window, a quantitative monitoring platform, and an investigational intervention entry point in Alzheimer’s disease. However, clinical translation of these applications requires standardized acquisition protocols, prospective longitudinal validation, and robust mechanistic evidence. To advance this agenda, we identify three priorities: multimodal data integration, closed-loop neuromodulation strategies, and methodologically rigorous validation frameworks.