Retina study eyes Alzheimer’s processes to target for early screening
Adding to other studies looking to the visual system, researchers peering into postmortem eye tissue have identified molecular and cellular changes that point toward possible development of a noninvasive exam for the early screening and monitoring of Alzheimer’s disease.
The NIH-funded research, published in Acta Neuropathologica, describes three Alzheimer’s-related processes occurring in the retina, the light-sensitive tissue in the back of the eye: 1) loss of pericytes, cells that regulate blood flow in tiny vessels and help form the blood-retina barrier, which protects the retina from harmful substances entering through the bloodstream; 2) reduced signaling by platelet-derived growth factor receptor-β (PDGFRβ), a protein that provides instructions for tissue maintenance and repair; and 3) accumulation of amyloid deposits in the retinal pericytes and blood vessels. The scientists, from Cedars-Sinai Medical Center, Los Angeles, also mapped these changes to specific regions and layers of the retina.
For the study, which built on prior research, the research team compared eye specimens from people who had died with Alzheimer’s disease or mild cognitive impairment (MCI) with eye specimens from people who had been cognitively normal. In total, scientists studied samples from 62 donors as well as brain specimens from a subset of donors. For each eye specimen, the researchers studied the retina’s blood vessel structure, using an immunofluorescent staining technique and transmission electron microscopy.
The researchers found greater pericyte loss, reduced PDGFRβ signaling, and more amyloid accumulation in the retinas of people who had been diagnosed with Alzheimer’s or MCI than in the retinas of cognitively normal donors. Each of these changes has been previously reported in the brain of people with Alzheimer’s disease. The changes in the retina were correlated with changes in the brain related to Alzheimer’s disease and cognitive decline.
The researchers noted that several other diseases affecting blood vessels in the retina, such as diabetic retinopathy and age-related macular degeneration, are characterized by a similar degradation of the blood-retina barrier. Discovery of the specific cellular and molecular changes related to this degradation could shed light on common aspects of Alzheimer’s and retinal disease processes. In addition, insights from this study could contribute to the use of retinal imaging to screen for and monitor Alzheimer’s in a way that is less expensive and less invasive than current neuroimaging methods.
This research was funded in part by NIA grants R01AG055865, R01AG056478, and R01EY13431.
These activities relate to NIA’s AD+ADRD Research Implementation Milestone 9.F. “Initiate studies to develop minimally invasive biomarkers for detection of cerebral amyloidosis, AD and AD-related dementias pathophysiology.”
Reference: Shi H, et al. Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina. Acta Neuropathologica. Published online Feb. 10, 2020. doi: 10.1007/s00401-020-02134-w.