The Alzheimer’s Maze
Oct 29, 2021 Susie Wampler, Photo Illustration, Bill Pollard
Nearly 6 million Americans are living with Alzheimer’s disease—and ultimately dying from it. With a cure remaining elusive, the challenge is to diagnose Alzheimer’s early so its harm can be delayed.
However, few ways to detect early Alzheimer’s disease are available and "clinical diagnosis has been largely focused on behavior and cognitive function," according to neuroscientist Maya Koronyo-Hamaoui, PhD, an associate professor in the Department of Neurosurgery. "Visual dysfunctions in Alzheimer’s are severely understudied." So she set about inventing a potentially better approach to assess whether vision impairment could be linked to cognitive decline.
With her Cedars-Sinai colleagues Yosef Koronyo, MSc, LLB, and Keith L. Black, MD, chair of Neurosurgery, director of the Maxine Dunitz Neurosurgical Institute, and the Ruth and Lawrence Harvey Chair in Neuroscience, Koronyo-Hamaoui devised a testing maze for mice with Alzheimer’s that could identify visual deficits and lead to better techniques for early diagnosis. Their x-shaped creation, the visual-stimuli four-arm maze (ViS4M), features programmed lights of various colors and intensities, along with grayscale objects.
The device builds on the researchers’ previous discoveries about Alzheimer’s effects on the eye’s retina. “Our studies have shown that retinal abnormalities and visual impairments can appear early in the disease,” Koronyo-Hamaoui says.
To examine sight-related changes that occur in mice with Alzheimer’s and compare them with their healthy brethren, the ViS4M’s different color wavelengths each activate a unique population of retinal cells—known as photoreceptor subtypes—that are important for different visual functions and color discrimination. The grayscale shapes are used to assess the mice’s ability to differentiate between an object and its surroundings.
Once in the ViS4M, mice could freely explore its corridors, with no treats or inducements to attract them to one route over another. As the mice entered and re-entered the maze, investigators collected data about their subjects’ response to color and contrast stimuli, speed of progress and cognitive function.
In a study published in Nature Scientific Reports, the investigators found that normal mice explored the maze’s corridors in specific patterns, suggesting that they remembered the arms previously visited and also detected changes in color and intensity of light.
By contrast, the Alzheimer’s-model mice were less able to alternate and transitioned more often between the same two arms. Repetitious movements made by these mice were not random but instead were linked to wavelength- and intensity-specific loss of visual discrimination. This mirrors the defects documented in some Alzheimer’s patients.
Mazes have long been used in Alzheimer’s research. The disease itself seems like an inescapable maze of constantly shifting paths and dead ends that eventually break down the mind and body.
The ViS4M represents a step forward by identifying “early and progressive impairments in color vision and contrast sensitivity in the mice with Alzheimer's,” Koronyo-Hamaoui notes.
Going forward, she adds, the ViS4M could enable vision and cognitive-behavioral scientists to make discoveries in rodent studies that could potentially be translated to improved human visual testing and early diagnosis of Alzheimer's.