Alzheimer’s Disturbed Sleep Traced to Eye Disorder

Researchers discovered a potential cause for the disrupted sleep patterns observed in Alzheimer’s disease patients. The study, “Melanopsin retinal ganglion cell loss in Alzheimer’s disease,” associates the degradation of a subset of eye cells involved in circadian rhythm regulation with the sleep dysfunction observed in AD, and was published in Annals of Neurology.

Melanopsin retinal ganglion cells (mRGCs), part of the eye’s photoreceptors, are sensors involved in light perception and in communication with the brain’s regions involved in circadian rhythms, the body’s physiological clock essential for processes such as sleep cycles. To investigate if the marked sleep disorder observed in Alzheimer’s patients was related to mRGC damage, Dr. Chiara La Morgia, a neuroscientist at the University of Bologna in Italy, and colleagues studied the prevalence and state of mRGCs through histological assays of the retinal tissue from 30 deceased organ donors. They also looked for the presence of amyloid beta, a protein involved in Alzheimer’s pathogenesis that is known to build in the brains of AD patients.

The results showed that donors with Alzheimer’s had 24% less melanopsin cells in their retinal tissue. Furthermore, cells from these donors had different morphologies and sizes, forming smaller and thinner threads crossing the retina. Tissue from healthy donors, in contrast, presented a higher prevalence of melanopsin cells, with rounder bodies and longer and thicker networks across the retina. In addition, fluorescent dyes showed accumulations of amyloid beta around damaged melanopsin cells.

It was not determined where in the Alzheimer’s pathogenesis timeline these cells are damaged — whether before disease onset or after neurodegeneration begins. However, the researchers believe their discovery has the potential to impact both the diagnosis and treatment of Alzheimer’s, while helping with the management of sleep disturbances in patients through the stimulation of remaining healthy cells.  As noted in a news release by co-author Dr. Maya Koronyo-Hamaoui, from the Cedars-Sinai Medical Center, sleep disturbances in AD patients represent a vicious cycle, further damaging the immune system and making it less effective at clearing the toxic proteins that cause neuronal death.

Should future research prove the correlation between mRGC dysfunction and sleep disturbances in living patients, scientists might be able to approach mRGCs as the cause of sleep symptoms in AD patients “and not just something that shows up alongside them.”