"Our study indicates that retinal pericytes underwent early programmed cell death in Alzheimer’s patients," Koronyo-Hamaoui said. Deficiency in vascular PDGFR? was tightly connected with increased brain levels of amyloid-beta buildup, including on the walls of brain arteries, and loss of cognitive function in those patients.
"We know that vascular flow and function are critical for cognitive function, and this study is the first to provide the molecular and cellular mechanisms," Koronyo-Hamaoui said.
The retinal abnormalities detected in the new study also were found in the patients with mild cognitive impairment. Taken together, these findings offer significant insights into how Alzheimer's develops, with major clinical implications, according to Keith L. Black, MD, professor and chair of the Department of Neurosurgery at Cedars-Sinai.
"The discovery of abnormalities in retinal blood vessels in patients with mild cognitive impairment holds the potential for diagnosing Alzheimer's years before people show symptoms," Black said. "Such early detection could provide insights into the disease and enable treatments to be created."
Black was a co-author of the new study. Haoshen Shi, MD, PhD, a postdoctoral scientist in Koronyo-Hamaoui's laboratory, was the first key author, and Yosef Koronyo, a research associate, was the second key author. Co-authors included researchers from the USC Keck School of Medicine and the Doheny Eye Institute in Los Angeles.
The next step for the researchers is to pursue further development of noninvasive high-resolution retinal imaging, potentially targeting pericytes and the molecular changes they discovered in blood vessels, as a means to diagnose Alzheimer's.
Funding: Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under award numbers R01 AG055865, R01 AG056478 and R01 EY13431 and by The Saban and The Marciano Private Foundations.
Conflict of interest: Koronyo, Koronyo-Hamaoui and Black are co-founders and stockholders of NeuroVision Imaging, Inc., 1395 Garden Highway, Suite 250, Sacramento, CA 95833, USA. Alexander Ljubimov and Black are stockholders and/or officers of Arrogene Nanotechnology, Inc., 8560 West Sunset Boulevard, Suite 424, Los Angeles, CA 90069, USA.