The burden of Alzheimer’s disease (AD) goes far beyond the afflicted patient, affecting family, friends, and a significant portion of the healthcare system. Currently, there are more than 5 million individuals living with AD in the U.S., incurring $259 billion in healthcare costs. With costs estimated to rise to $1.1 trillion by 2050 as the number of AD cases could surpass 16 million, it is imperative that diagnostic tests be developed to detect early warning signs that signal the onset of the disease—at the very least to allow patients and their family time to prepare for various eventualities.
Now, a team of neuroscientists at Cedars-Sinai have developed a noninvasive eye scan that could potentially detect the key signs of AD years before patients experience symptoms. Findings from the study—published recently in JCI Insight in an article entitled “Retinal Amyloid Pathology and Proof-of-Concept Imaging Trial in Alzheimer’s Disease”—showed that investigators were able to detect the buildup of amyloid-beta (Aβ) protein on the retina of AD patients. The results from this new study represent a major advancement toward identifying people with an elevated risk for the debilitating condition years sooner.
“The findings suggest that the retina may serve as a reliable source for Alzheimer's disease diagnosis,” explained senior study author Maya Koronyo-Hamaoui, Ph.D., associate professor in the departments of neurosurgery and biomedical sciences at Cedars-Sinai. “One of the major advantages of analyzing the retina is the repeatability, which allows us to monitor patients and potentially the progression of their disease.”
Interestingly, the researchers noted that another key finding was the discovery of amyloid plaques in previously overlooked peripheral regions of the retina. The authors pointed out that the plaque amount in the retina correlated with plaque amount in specific areas of the brain. “Now we know exactly where to look to find the signs of AD as early as possible,” remarked lead study author Yosef Koronyo, M.Sc., a research associate in the department of neurosurgery at Cedars-Sinai.
“Our hope is that eventually the investigational eye scan will be used as a screening device to detect the disease early enough to intervene and change the course of the disorder with medications and lifestyle changes,” added co-senior study investigator Keith Black, M.D., chair of Cedars-Sinai's department of neurosurgery and director of the Maxine Dunitz Neurosurgical Institute.
For decades, the only way to officially diagnose AD was to survey and analyze a patient's brain after the patient died. In recent years, physicians have relied on positron emission tomography (PET) scans of the brains of living people to provide evidence of the disease. However, this technology is expensive and invasive, requiring the patient to be injected with radioactive tracers.
For the current study, the researchers conducted a clinical trial on 16 AD patients who drank a solution that includes curcumin, a natural component of the spice turmeric. The curcumin causes amyloid plaque in the retina to “light up” and be detected by the scan. The patients were then compared to a group of younger, cognitively normal individuals.
“Burden, distribution, cellular layer, and structure of retinal Aβ plaques were analyzed in flat mounts and cross-sections of definite AD patients and controls (n = 37),” the authors wrote. “In a proof-of-concept retinal imaging trial (n = 16), amyloid probe curcumin formulation was determined and protocol was established for retinal amyloid imaging in live patients.”
The authors added that “histological examination uncovered classical and neuritic-like Aβ deposits with increased retinal Aβ42 plaques (4.7-fold; P = 0.0063) and neuronal loss (P = 0.0023) in AD patients versus matched controls. Retinal Aβ plaque mirrored brain pathology, especially in the primary visual cortex (P = 0.0097 to P = 0.0018; Pearson’s r = 0.84–0.91).”
To find a more cost-effective and less invasive technique, the Cedars-Sinai team collaborated with investigators at NeuroVision Imaging, the Commonwealth Scientific and Industrial Research Organization (CSIRO), the University of Southern California, and UCLA to translate their noninvasive eye screening approach to humans.
The investigators were excited by their findings and are in the process of expanding their study to incorporate a much larger number of subjects.