Published on: December 12, 2015
by Lindzi Wessel for ScienceMag:
Nighttime restlessness is common among people with Alzheimer’s, and many stay awake agitated and pacing long after their family members have gone to sleep. Now, scientists may have figured out why: The disease appears to degrade a special type of eye cell that tells the brain when it’s day or night. If the discovery holds up, it might offer clinicians a new way to monitor the progression of Alzheimer’s and could lead to treatments that restore a good night’s sleep.
The cells in question are known as melanopsin retinal ganglion cells. They send signals to the brain center responsible for , our body’s daily clock. The cells make up 1% to 2% of the eye’s light-responsive sensors, but they play no role in vision, says lead author Chiara La Morgia, a neuroscientist at the University of Bologna in Italy. Rather, they sense light levels around us, telling us when to get sleepy and when to be alert.
La Morgia and her colleagues, aware of the profound sleep problems often seen in Alzheimer’s, wondered whether the cells may stop doing their job as the disease progresses. “If you lose them, you should see dysfunction of the circadian rhythms and see disrupted sleep,” says Alfredo Sadun, neuro-opthamologist at the University of California, Los Angeles, and co-author of the study. “That is the exact symptomology we see in Alzheimer’s disease.”
To learn more, the researchers used dyes to mark melanopsin cells in the eyes of 30 recently deceased organ donors. They found approximately 24% fewer melanopsin cells in the eyes of people with Alzheimer’s than in the eyes of donors without the disease. What’s more, the melanopsin cells in those with Alzheimer’s looked different. Healthy melanopsin cells have round cell bodies with many long threads criss-crossing the retina like the remnants of a spider’s abandoned web. In people with Alzheimer’s, the cells were stubbier, with thinner threads that cast a smaller network, the team will report in an upcoming issue of Annals of Neurology.
To search for clues that might help explain the cells’ degeneration, the scientists used fluorescent dyes to inspect the retinal tissue for a protein called amyloid β, which builds up in the brains of people with Alzheimer’s. They found this toxic protein accumulated around the degrading melanopsin cells.
The researchers can’t yet say whether melanopsin cells break down in those with Alzheimer’s before the disease attacks other parts of the brain or whether signals from a degenerating brain shrivel the cells, says co-author Valerio Carelli, a neuroscientist at the University of Bologna. However, he believes the findings may influence both treatment and diagnosis of the disease. The retina is the only part of the brain that isn’t covered by the skull, Carelli notes, meaning researchers can easily assess it. Developing tools that allow clinicians to observe the amount of amyloid β in the eye or the change in melanopsin cell function over time could help them monitor the disease, he says.
Finding ways to preserve these cells or to better stimulate remaining cells could also help alleviate sleep disturbances in at least some patients, says co-author Maya Koronyo-Hamaoui, a neuroimmunologist at the Cedars-Sinai Medical Center in Los Angeles, California. She notes that sleep disturbances may drive a “vicious cycle,” in which poor rest disrupts the immune system, which may make immune cells less efficient at clearing toxic proteins.
The study provides a mechanistic explanation for “an aspect of the disease that is often overlooked,” says cell biologist Jeremy Sivak of the University of Toronto in Canada, who was not involved with the work. He is eager to see the next step: a study that correlates dysfunction in these cells to severity of sleep symptoms in the same group of living patients. This demonstration, he says, will be necessary before researchers can be sure that melanopsin cell damage is behind the sleep disturbances in people with Alzheimer’s, and not just something that shows up alongside them.
Photo: Melanopsin cells in a normal human retina. Credit: Jens Hannibal
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