Cedars-Sinai investigators have produced essentially the most extensive evaluation thus far of changes within the retina-;a layer of tissue in the back of the attention where visual information originates-;and the way those retinal changes correspond to brain and cognitive changes in Alzheimer’s disease patients.

Their evaluation, published within the peer-reviewed journal Acta Neuropathologica, is a vital step toward understanding the complex effects of Alzheimer’s disease on the retina, especially on the earliest stages of cognitive impairment. Experts imagine this understanding is vital for the event of more practical treatments that might prevent progression of the disease.

Greater than 3 million Americans are diagnosed with Alzheimer’s disease every year. The disease progressively destroys memory and cognitive ability. Currently, there is no such thing as a single diagnostic test that may definitively diagnose a patient with Alzheimer’s disease, and the latest treatments only slow–don’t stop-;progression.

Our study is the primary to offer in-depth analyses of the protein profiles and the molecular, cellular, and structural effects of Alzheimer’s disease within the human retina and the way they correspond with changes within the brain and cognitive function. These findings may eventually result in the event of imaging techniques that allow us to diagnose Alzheimer’s disease earlier and more accurately and monitor its progression noninvasively by searching through the attention.”

Maya Koronyo-Hamaoui, PhD, professor of Neurosurgery, Neurology, and Biomedical Sciences at Cedars-Sinai and senior writer of the study

“The retina, a developmental extension of the brain, offers an unparalleled opportunity for inexpensive, noninvasive monitoring of the central nervous system,” said Yosef Koronyo, MSc, research associate within the Cedars-Sinai Department of Neurosurgery and first writer of the study. “And with the assistance of our collaborators, we discovered the buildup of highly toxic proteins within the retinas of patients with Alzheimer’s disease and mild cognitive impairment, causing severe degeneration of cells.”

Investigators checked out retinal and brain tissue samples collected over 14 years from 86 human donors-;the most important group of retinal samples from human patients with Alzheimer’s disease and mild cognitive impairment to date studied. They compared samples from donors with normal cognitive function to those with mild cognitive impairment on the earliest stages of Alzheimer’s disease, and people with later-stage Alzheimer’s disease dementia.

The investigators explored the physical features of the retinas of those patients, measuring and mapping markers of inflammation and functional cell loss, and analyzed the proteins present in retinal and brain tissues.

Here’s what investigators present in the retinas of patients with mild cognitive impairment and Alzheimer’s disease:

• An overabundance of a protein called amyloid beta 42, which within the brains of Alzheimer’s disease patients clumps together to form plaques that disrupt 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 astrocytes and immune cells, called microglia, 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 accountable for inflammation, and cell and tissue death

“These changes within 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 Koronyo.

Retinal changes also correlated with the pathological stage of Alzheimer’s disease (called Braak stage) and patients’ cognitive status. And so 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 results 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 within the brain and will be detected within the earliest stages of impairment, they might lead us to latest diagnostics for Alzheimer’s disease and a method to guage latest types of treatment.”

Source:

Cedars-Sinai Medical Center

Journal reference:

Koronyo, Y., et al. (2023) Retinal pathological features and proteome signatures of Alzheimer’s disease. Acta Neuropathologica. doi.org/10.1007/s00401-023-02548-2.