Noninvasive retinal imaging may detect signs of Alzheimer's disease

In the future, early diagnosis and effective monitoring of Alzheimer’s disease (AD) may be possible via noninvasive detection of retinal ß-amyloid deposits—a hallmark of Alzheimer’s disease—in living patients. To this end, researchers at Cedars-Sinai, Los Angeles, CA, and NeuroVision Imaging LLC, Sacramento, CA, have demonstrated proof of concept for an experimental optical imaging system that detects retinal ß-amyloid. Their results were published online in the Journal of Clinical Investigation Insight.

“This is the first study demonstrating the potential to image and quantify retinal findings related to ß-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 ß-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 senior author Maya Koronyo-Hamaoui, PhD, associate professor of neurosurgery and biomedical sciences and a research scientist, Maxine Dunitz Neurosurgical Institute, Cedars-Sinai, and a co-founder, inventor and scientist at NeuroVision.

AD patients exhibit numerous retinal pathologies, including amyloid ß-protein (Aß) deposits, and therefore, Dr. Koronyo-Hamaoui and colleagues sought to assess whether noninvasive detection of such pathologies could also detect AD.

Previously, lead author Yosef Koronyo, research associate, Cedars-Sinai, and scientist and inventor, NeuroVision, had conducted the study that became the basis for this proof-of-concept study.

“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,” explained Koronyo.

After modifying the device for use in humans, they took flat mounts and cross sections from 23 deceased patients with definite AD and 14 controls, and analyzed burden, distribution, cellular layer, and structure of retinal Aß plaques.

For their proof-of-concept retinal imaging trial, they included 16 patients in whom amyloid probe curcumin formulation was determined and established a protocol for retinal amyloid imaging for use in live patients.

Upon histological exam, they found classic and neuritic-like Aß deposits with increased retinal Aß42 plaques in patients with AD compared with matched controls (4.7-fold increase; P=0.0063) as well as significant neuronal loss (P=0.0023).

In addition, Dr. Koronyo-Hamaoui, Koronyo, and their colleagues observed that retinal Aß plaque mirrored brain pathology, particularly in the primary visual cortex (P=0.0097 to P=0.0018; Pearson’s r=0.84-0.91).

Retinal deposits were often associated with blood vessels and occurred in ‘hot spot’ peripheral regions of the superior quadrant and innermost retinal layers. Furthermore, retinal Aß was found to assemble into protofibrils and fibrils via transmission electron microscopy. 

Researchers also demonstrated the possibility of imaging retinal amyloid deposits with solid-lipid curcumin and a modified scanning laser ophthalmoscope in live patients. They constructed a fully automated calculation of the retinal amyloid index (RAI), which is a quantitative measure of increased curcumin fluorescence. Using RAI scores, they demonstrated a 2.1-fold increase in AD patients compared with controls.

“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,” said Keith L. Black, MD, chairman, NeuroVision, chair of the Department of Neurosurgery, and director of the Maxine Dunitz Neurosurgical Institute at Cedars-Sinai. “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.”

This study was funded by the National Institute on Aging and The Saban and The Marciano Family Foundations.