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Researchers ID Retinal Changes That Correspond to Brain Changes in Early-Stage Alzheimer’s Disease
Researchers have produced the most extensive analysis to date of changes in the retina and how those retinal changes correspond to brain and cognitive changes in patients with Alzheimer’s disease.
The analysis, published in Acta Neuropathologica, is an important step toward understanding the complex effects
“Our study is the first to provide in-depth analyses of the protein profiles and the molecular, cellular, and structural effects of Alzheimer’s disease in the human retina and how they correspond with changes in the brain and cognitive function,” said senior author Maya Koronyo-Hamaoui, PhD, Cedars-Sinai Medical Center, Los Angeles, California. “These findings may eventually lead to the development of imaging techniques that allow us to diagnose Alzheimer’s disease earlier and more accurately and monitor its progression noninvasively by looking through the eye.”
“The retina, a developmental extension of the brain, offers an unparalleled opportunity for affordable, noninvasive monitoring of the central nervous system,” said first author Yosef Koronyo, MSc Cedars-Sinai. “And with the help of our collaborators, we discovered the accumulation of highly toxic proteins in the retinas of patients with Alzheimer’s disease and mild cognitive impairment, causing severe degeneration of cells.”
The investigators looked at retinal and brain tissue samples collected over 14 years from 86 human donors -- the largest group of retinal samples from human patients with Alzheimer’s disease and mild cognitive impairment thus far studied. They compared samples from donors with normal cognitive function to those with mild cognitive impairment at the earliest stages of Alzheimer’s disease, and those with later-stage Alzheimer’s disease dementia. The investigators explored the physical features of the retinas of these patients, measuring and mapping markers of inflammation and functional cell loss, and analysed the proteins present in retinal and brain tissues.
Here is what investigators found in the retinas of patients with mild cognitive impairment and Alzheimer’s disease:
- An overabundance of amyloid beta 42, which disrupts brain function.
- Accumulation of amyloid beta protein in ganglion cells, the cells that bridge visual input from the retina to the optic nerve.
- Higher numbers of microglia cells tightly surrounding amyloid beta plaques.
- As many as 80% fewer microglial cells clearing amyloid beta proteins from the retina and brain.
- Specific molecules and biological pathways responsible for inflammation, and 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,” said Dr. Koronyo-Hamaoui.
Retinal changes also correlated with the pathological stage of Alzheimer’s disease -- Braak stage -- and patients’ cognitive status. In addition, the retinal changes 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, Cedars-Sinai. “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.”
Reference: https://link.springer.com/article/10.1007/s00401-023-02548-2
SOURCE: Cedars-Sinai Medical Center
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