The nerve cell-damaging plaque that builds up in the brain with Alzheimer's disease also builds up in the retinas of the eyes -- and it shows up there earlier, leading to the prospect that noninvasive optical imaging of the eyes could lead to earlier diagnosis, intervention and monitoring of the disease, according to new research.
Scientists discovered characteristic amyloid plaques in retinas from deceased Alzheimer's disease patients and used a noninvasive optical imaging technique to detect retinal plaques in live laboratory mice genetically modified to model the human disease. The combined results suggest the possibility that noninvasive retinal imaging may be helpful in early diagnosis of the disease.
The research was conducted by a team of scientists at Cedars-Sinai Medical Center in collaboration with colleagues from the Weizmann Institute of Science in Israel and the University of Southern California. Results were published online June 13 in the journal NeuroImage, and related findings will be presented July 13 at the Alzheimer's Association International Conference on Alzheimer's Disease.
Alzheimer's disease is a devastating condition that is becoming more prevalent worldwide as the baby-boom generation advances into its senior years, but there is no conclusive, noninvasive way to diagnose it. Previous studies have suggested that changes in the brain may begin years or even decades before symptoms occur -- emphasizing the need for earlier, reliable detection for early therapeutic intervention to achieve effective remedy. The new study suggests the possibility of monitoring Alzheimer's disease through a simple retinal imaging approach.
Abnormal deposits in the brain called beta-amyloid plaques, which damage cells and interrupt cell-to-cell communications, are recognized as a hallmark sign of the disease. However, because existing noninvasive brain-imaging technologies cannot provide sufficient detail about these changes, the most definitive diagnosis of Alzheimer's disease comes after an autopsy.
The research team considered the retina a better target for noninvasive imaging of Alzheimer's disease because it is readily accessible and, unlike other components of the eye, it is part of the central nervous system, having a direct connection and thus many similarities with the brain. Previous studies have documented non-specific visual disturbances, eye disorders and certain types of retinal abnormalities occurring with Alzheimer's disease and other neurodegenerative conditions, but this is the first to identify human retinal plaque deposits that could provide a specific diagnostic marker of Alzheimer's disease.
Among the new findings:
Together, the results offer the first evidence for the existence of Alzheimer's-specific plaques in the retina of human patients and the ability to detect individual plaques in live mouse models, creating a strong basis for future research building on these findings. According to the authors, these studies establish the potential of direct retinal beta-amyloid plaque imaging in live subjects as a tool for early Alzheimer's disease diagnosis and prognosis, as well as assessment of therapies.
Specialists in neurosurgery, ophthalmology, imaging systems, neuroimmunology, pathology, neurology and biomedical engineering collaborated on these studies, which were conducted at Cedars-Sinai Medical Center by scientists from Cedars-Sinai, the Weizmann Institute of Science in Israel, and the University of Southern California.
The journal article's first authors are Maya Koronyo-Hamaoui, Ph.D., a research scientist and assistant professor of neurosurgery at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute and a principal investigator in the Neuroimmunology Laboratory at Cedars-Sinai; and Yosef Koronyo, M.Sc., LL.B., a research associate in the departments of Surgery and Neurosurgery at Cedars-Sinai. Michal Schwartz, Ph.D., visiting professor in the Department of Neurosurgery at Cedars-Sinai, and the Ilze and Maurice Professorial Chair of Neuroimmunology at the Weizmann Institute of Science in Rehovot, Israel, is a senior author.
The work was supported by the Marciano Family Foundation, the Maxine Dunitz Neurosurgical Institute, the U.S. Navy Bureau of Medicine and Surgery, the National Eye Institute, the Winnick Family Foundation, and a National Institute on Aging grant to the University of Southern California Alzheimer's Disease Research Center.
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