The study by Gaire et al. provides an in-depth examination of the increasing evidence linking Alzheimer's disease (AD) to a retinal pathology. It highlights the retina's potential as a noninvasive biomarker for the early detection and monitoring of AD. The presence of amyloid-β plaques, tau protein abnormalities, and neuroinflammation in the retinas of patients with AD mirrors the pathology observed in their brain. Numerous studies have confirmed the existence of amyloid-β deposits in the inner retinal layers of patients with AD, which are akin to those in the brain. The tau protein abnormalities, including phosphorylated tau, contribute to neuronal damage and cognitive decline. Furthermore, the retinal inflammation is marked by glial cell activation and elevated levels of inflammatory markers.

Various ophthalmic imaging techniques, such as optical coherence tomography (OCT) and fundus autofluorescence (FAF), have been employed to identify retinal changes in patients with AD. These alterations include retinal thinning, vascular abnormalities, and disruptions in the function of the retinal pigment epithelium. These findings indicate that the retina is highly susceptible to the AD pathology and that these processes may occur concurrently in the brain and retina due to their shared embryonic origin and neurovascular anatomy. Proteomics analysis has revealed a comparable pattern of dysregulated proteins and biological pathways in the retina and brain of patients with AD. These patterns are characterized by heightened inflammatory and neurodegenerative processes, impaired oxidative phosphorylation, and mitochondrial dysfunction.

Due to the advancements in imaging technologies, AD-specific amyloid deposits, vasculopathy, and neurodegeneration can be detected in the retinas of living patients with AD. These findings imply alterations at different stages of the disease and correlations with the brain pathology. Current and exploratory ophthalmic imaging modalities, such as OCT-angiography, confocal scanning laser ophthalmoscopy, and hyperspectral imaging, have demonstrated potential in the clinical assessment of patients with AD. The noninvasive nature of retinal imaging makes it an appealing target for developing early diagnostic biomarkers for AD, and with their aid, we could identify AD-related changes in the retina before cognitive symptoms manifest.

Despite the potential of using retinal imaging to diagnose AD, further studies are required to comprehensively understand the relationship between the retinal pathology and AD. Furthermore, the specific mechanisms underlying the accumulation of amyloid-β and tau in the retina, as well as the role of neuroinflammation in the disease progression, should be investigated. Additional studies are also necessary to evaluate the sensitivity and specificity of retinal imaging techniques for the early detection of AD. Future studies should also focus on developing more sensitive and specific retinal biomarkers for AD and exploring the mechanisms underlying the retinal pathology in AD.

In conclusion, the article provides valuable insights into the current state of research on the pathophysiology of retinal changes in patients with AD. The study's findings suggest that the retina is a promising target for development as a noninvasive biomarker for the early detection and monitoring of AD. Nonetheless, further study is required to fully elucidate the relationship between the retinal pathology and AD and develop clinically useful biomarkers.

Article reference of the review: Gaire BP, Koronyo Y, Fuchs DT, Shi H, Rentsendorj A, Danziger R, et al. Alzheimer's disease pathophysiology in the Retina. Prog Retin Eye Res. 2024 Jul 1;101:101273.