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Peering Closer at Retinal Damage May Uncover Early Indicator of Alzheimer Disease
Retinal changes may align with brain and cognitive changes in Alzheimer disease (AD) patients, according to a team of Cedars-Sinai researchers who have completed an extensive histopathological and biochemical investigation of postmortem retina and brain tissue. Findings were published in Acta Neuropathologica.
“Our study is the first to provide in-depth analyses of the protein profiles and the molecular, cellular, and structural effects of Alzheimer disease in the human retina and how they correspond with changes in the brain and cognitive function,” said senior author Maya Koronyo-Hamaoui, PhD, professor of Neurosurgery, Neurology, and Biomedical Sciences at Cedars-Sinai in a news release. “These findings may eventually lead to the development of imaging techniques that allow us to diagnose Alzheimer disease earlier and more accurately and monitor its progression noninvasively by looking through the eye.”
The researchers examined retinal and brain tissue samples from 86 donors collected over a 14 year period. The samples were divided into 3 groups (normal cognitive function, mild cognitive impairment in early stages of AD, and later-stage AD dementia) and compared to better understand the pathological features of AD in the retina. Measures included physical retinal features, measuring and mapping inflammation markers alongside functional cell loss, and analysis of the proteins present in both tissue types.
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Results showed the following distinctions between the retinal tissue of patients with normal cognitive function versus those with mild cognitive impairment and/or more advanced Alzheimer disease:
- An overabundance of amyloid beta 42—a protein present in AD patient brains that clumps together in plaques to disrupt brain function;
- Amyloid beta protein accumulated in ganglion cells, which communicate visual input to the optic nerve;
- High amounts of microglia tightly clustered around the amyloid beta plaques;
- Up to 80% microglial cells were working to clear amyloid beta proteins from the retina and brain; and
- Distinct molecules and biological pathways were causing inflammation as well as cell and tissue death.
“These changes in the retina correlated with changes in parts of the brain called the entorhinal and temporal cortices, a hub for memory, navigation and the perception of time,” noted first author Yosef Koronyo, MSc, research associate, Department of Neurology, Cedars-Sinai.
The authors also found that retinal changes correlated with the AD pathological stage and patients’ cognitive status. Retinal changes were also observed in patients who appeared cognitively normal or who experienced mild cognitive impairment. Thus, the changes may serve as a potential early indicator of future cognitive decline.
“Taken together, our findings provide novel and deeper understanding of the susceptibility of the retina to AD processes, including molecular, cellular, and structural abnormalities that can be detected in the earliest stages of functional impairment,” the authors wrote in the study conclusion. “Furthermore, our study has identified the pathological connections between the retina, brain, and cognition, proposing that the retina could serve as a reliable biomarker for non-invasive AD detection and monitoring.”
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