By Linda Conlin, Pro to Pro Managing Editor

Once again, the eye can reveal the body’s secrets. In a recent analysis, Retinal pathological features and proteome signatures of Alzheimer’s disease, published in Acta Neuropathologica, Cedars-Sinai investigators looked at post mortem retinal and brain tissue samples collected over 14 years from 86 human donors and compared samples from donors with normal cognitive function to those with mild cognitive impairment at the earliest stages of Alzheimer’s disease, as well as those with later-stage dementia. (Koronyo, Y., Rentsendorj, A., Mirzaei, N. et al. Retinal pathological features and proteome signatures of Alzheimer’s disease. Acta Neuropathol (2023).

In Alzheimer’s disease, the amyloid beta 42 protein clumps to form plaques that compromise brain function. The eye is an extension of the brain, and this protein was found in the retinal ganglion cells of patients with mild cognitive impairment and Alzheimer’s disease. (Retinal ganglion cell axons in the inner margin of the retina, make up the optic nerve and project from the retina to the brain.) Noninvasive retinal optical imaging already has been used to detect amyloid plaques, atrophy, and vascular damage in living Alzheimer’s disease patients. The investigators hypothesized that amyloid protein accumulation, associated gliosis (the response of neural tissue to injury) and neurodegeneration, occur in the retina at the onset of functional impairment. They predicted that the degree of retinal pathology indicates the severity of brain pathology and cognitive decline.

Indeed, they found that the severity of plaques in all brain regions significantly correlated with retinal plaques, degeneration of photoreceptor pathways, and retinal thinning. Results were consistent across age and gender. The team postulates that, like highly energy-demanding brain regions such as the medial temporal cortex for memory, navigation and time perception, photoreceptors are especially vulnerable to Alzheimer’s disease processes. Retinal changes also correlated with the pathological stage of Alzheimer’s disease (called Braak stage) and patients’ cognitive status. And they were found even in patients who appeared cognitively normal or very mildly impaired, marking them as a possible early predictor of later cognitive decline.

“These findings give us a deeper understanding of the effects of Alzheimer’s disease on the retina,” said Keith L. Black, MD, chair of the Department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai and a co-author of the study. “Because these changes correspond with changes in the brain and can be detected in the earliest stages of impairment, they may lead us to new diagnostics for Alzheimer’s disease and a means to evaluate new forms of treatment.” What’s more, the retina could serve as a reliable biomarker for non-invasive Alzheimer’s disease detection and monitoring.