Critical Next Steps for Translation of Preclinical and Ex Vivo Human Retinal Studies for Alzheimer’s Disease Diagnosis

Abstract

AbstractRetinal ganglion cells are part of the CNS and as such many years of research has focused on determining and documenting how changes in retinal cells and layers may inform on disease diagnosis, display neuropathology and neurodegeneration. As noted in this session, degeneration of the retina and visual dysfunction occur in the majority of AD, with new and exciting imaging techniques being employed in both animal models and human ex vivo retinal tissues that suggest that the retina can act as a mirror to the brain. Unfortunately, consistency of methods and access to viable tissues has hampered the generalizability and speed of translatability of these exciting fundings. In addition, to date, no studies have directly linked observed neuropathology or neurodegeneration in the retina with more established biomarkers in CSF or blood which is ultimately needed to understand whether retinal imaging or analysis is viable for clinical use. Retinal imaging in live participants could serve as a minimally invasive biomarker to detect neurodegenerative disease. From recent anti‐amyloid studies, identifying individuals at risk for AD in the asymptomatic stage is critical for efficacy of treatments. If validation and establishment of retinal analyses continue as they have and consistency and consensus is obtained in retinal targets to focus on and these prove to mirror changes ongoing in brain, the timing of these changes in relation to brain changes will need to be determined so that a window of when retinal imaging and analysis is viable will need to be determined. Once the conditions, methods and timing of retinal imaging is determined, the ultimate goal would be to screen aged individuals in a primary care setting annually and then refer to specialty clinics or centers for follow up, confirmation and consideration for therapeutic trials.