Retinal Imaging May Reveal Alzheimer’s Disease Signs

A noninvasive eye imaging technique can identify beta amyloid protein deposits that mirror those in the brain, a study led by researchers at Cedars-Sinai and NeuroVision Imaging LLC reports.

The work provides a scientific basis for using the experimental technology to detect the pathological hallmarks of Alzheimer’s.

Accumulations of neurotoxic beta-amyloid protein can be detected with positron emission tomography, or PET scans, and analysis of cerebrospinal fluid, but these are invasive, inconvenient and costly, making them impractical for routine screening and follow-up evaluation.

“This is the first study demonstrating the potential to image and quantify retinal findings related to beta-amyloid plaques noninvasively in living patients using a retinal scan with high resolution. This clinical trial is reinforced by an in-depth exploration of the accumulation of beta-amyloid in the retina of Alzheimer’s patients versus matched controls, and a comparison analysis between retina and brain pathologies. Findings from this study strongly suggest that retinal imaging can serve as a surrogate biomarker to investigate and monitor Alzheimer’s disease,”

said Maya Koronyo-Hamaoui, Ph.D.

Retinal Alzheimer’s Detection

Koronyo-Hamaoui, an associate professor of Neurosurgery and Biomedical Sciences and a research scientist at the Maxine Dunitz Neurosurgical Institute at Cedars-Sinai, and a co-founder, inventor and scientist at NeuroVision, is the senior leading author of the recently published article.

Keith L. Black, M.D., chairman of NeuroVision, chair of the Department of Neurosurgery and director of the Maxine Dunitz Neurosurgical Institute at Cedars-Sinai, explained:

“As a developmental outgrowth of the central nervous system that shares many of the brain’s characteristics, the retina may offer a unique opportunity for us to easily and conveniently detect and monitor Alzheimer’s disease.

We know that Alzheimer’s begins as many as 10 or 20 years before cognitive decline becomes evident, and we believe that potential treatments may be more effective if they can be started early in the process. Therefore, screening and early detection may be crucial to our efforts to turn the tide against the growing threat of this devastating disease.”

The study’s first author, Yosef Koronyo, a research associate at Cedars-Sinai and a scientist and inventor at NeuroVision, said the latest findings cap a decade of study that has produced several landmark discoveries.

“In 2010, our research group published an article providing the first evidence for the existence of Alzheimer’s-specific plaques in the human retina, and we demonstrated the ability to detect individual plaques in live mouse models using a modified ophthalmic device.”

pathological hallmarks of Alzheimer's disease

Shown here are the pathological hallmarks of Alzheimer’s disease, beta-amyloid plaques (brown spots), as seen both in brain and retinal tissues from deceased patients.
Image from JCI Insight. 2017; 2(16):e93621. doi:10.1172/jci.insight.93621

After adapting the technology for human application, the researchers initiated several ongoing clinical trials in the United States and Australia to determine the feasibility of detecting and quantifying beta-amyloid plaques in patients with the disease.

Autofluorescence Imaging

In the new article, the researchers describe a 16-patient clinical trial to demonstrate the feasibility of identifying beta-amyloid in the eye using autofluorescence imaging. The authors report:

  • A detailed analysis of beta-amyloid deposit types using electron microscopy.
  • The first report of certain Alzheimer’s-related pathologies in the retina, including vascular amyloid pathology.
  • The demonstration of a significant correlation between retinal and brain plaques, and coexistence of neuronal loss.
  • The first feasibility study for noninvasively detecting presumed amyloid deposits in retinas of living patients.
  • The demonstration of a fully automated calculation quantifying retinal autofluorescence that showed a 2.1-fold increase in patients with Alzheimer’s, compared with controls.

They also provide detailed analyses and several new findings on Alzheimer’s pathology in the retina, results of research with donated eyes and brains of 37 deceased patients, 23 with confirmed Alzheimer’s disease and 14 controls.

Among key findings, the researchers report a 4.7-fold increase in retinal plaque burden in patients with Alzheimer’s, compared to controls, and they provide observations regarding geometric distribution and layer location of amyloid pathology in the retina.

With the imaging technology’s ability to detect autofluorescence signal related to retinal beta-amyloid, these findings may lead to a practical approach for large-scale identification of the at-risk population and monitoring of Alzheimer’s, the researchers say.

Other insights reported include the first histologic quantitative analysis of retinal plaque clusters, or “hot spots,” containing the most toxic forms of beta-amyloid with specific distribution patterns in superior peripheral regions that were previously unexplored.

Funding for the work was provided by the National Institutes of Health/National Institute on Aging, The Saban Family Foundation and The Marciano Family Foundation.

Yosef Koronyo … Keith L. Black, Maya Koronyo-Hamaoui
Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease
JCI Insight. 2017;2(16):e93621. doi:10.1172/jci.insight.93621

Image: Virginia Tech