Fruit flies, or rather their tiny brains, can give us some clues about mysteries behind Alzheimer’s disease and how sleep loss plays a role.
A Washington State University researcher is studying the insect’s brain and the effect of sleep patterns, and recently was able to generate physiological characteristics similar to Alzheimer’s in fruit flies.
The results suggest sleep disturbance may be an early warning sign for Alzheimer’s, said Jason Gerstner, an assistant research professor at WSU’s Elson S. Floyd College of Medicine in Spokane. Findings also indicate the brain’s fatty acid binding protein, or FABP, could be key to reducing damaging effects of protein pieces called beta-amyloid that clump together and are associated with plaque forming in the brains of Alzheimer’s patients.
One day, further research could lead to discoveries to delay disease onset by using targeted treatments to increase sleep and slow symptoms such as neurodegeneration and memory loss that might be impacted by FABP, Gerstner said.
“A major reason why Alzheimer’s patients are often institutionalized is family and caregivers are no longer able to care for them because they’re up all the time and they have random sleep cycles,” Gerstner said. “As you age, there is also a normal decline in your sleep generally.”
“It seems with this disturbance in sleep, it’s exacerbated in preclinical Alzheimer’s disease. There is an association between sleep disturbance and this plaque formation. We don’t really understand the relationship, but it seems to be bidirectional.”
So it’s a vicious cycle. Or a perfect storm, as Gerstner says.
“Increased sleep disturbance seems to increase more of this beta-amyloid, and in turn this beta-amyloid seems to increase sleep disturbance,” he said.
Alzheimer’s disease is the nation’s sixth leading cause of death, according to the Alzheimer’s Association. It is a type of dementia that causes problems with memory, thinking and behavior. Symptoms usually develop slowly and get worse over time, becoming severe enough to interfere with daily tasks.
Scientists have known that Alzheimer’s patients commonly experience disturbed sleep. Gerstner’s study, published last summer in the Journal of Neuroscience Research, looked at the interaction between FABP and beta-amyloid in relation to sleep patterns, examining those dynamics in fruit flies.
“I’m sure people wonder, why fruit flies?” Gerstner said. “When you’re trying to uncover what these molecular mechanisms are that are so fundamental to all animals, one way to do that is to look at a simple organism like the common fruit fly.”
Seventy percent of known disease-causing genes are present in fruit flies, Gerstner added.
The study researched genetically manipulated flies with higher levels of beta-amyloid and compared them to a control group of unmodified flies. Gerstner and co-researchers observed significantly fragmented sleep in the beta-amyloid flies, at an age when they didn’t yet show signs of cognitive decline, the study said.
However, they saw improved sleep in a subgroup of the beta-amyloid flies that had an additional genetic manipulation increasing their FABP levels.
“The accumulation of beta-amyloid, progression of neurodegeneration, cognitive decline and reduced longevity — all those traits are observed in our Alzheimer’s flies, and it looks like fragmented sleep is an early marker,” he said.
What is known about fruit flies’ sleep patterns and how to measure their sleep? Those are questions co-researcher William Vanderheyden has grown to expect and he has an explanation down pat.
“Sleep has universal features,” Vanderheyden said. “With humans and sleep studies, you attach electrodes. You can’t do that in a fly, but when they’re sleeping, they are laying down, quiescent, not moving. Sleep in a fly is inverse of activity, so when they’re not moving for five minutes, we call that sleep.”
He said fruit flies also provide a powerful genetic tool, because of the ease of manipulating and screening multiple genes. The researchers plan similar studies on other neurological diseases, such as Parkinson’s.
Just as loud noises often wake people, tapping on a test tube filled with the flies jolts them from sleep. The researchers use a recording system with an infrared beam that measures flies’ activity and sleep.
Another tool is an apparatus that takes the tubes, rocks them down and snaps them back up. “We do that all night long,” for various sleep deprivation studies, Vanderheyden said.
In earlier research, Gerstner found that genetically manipulated fruit flies with higher FABP levels showed improved sleep and some long-term memory formation. His recent study took that research and paired it with knowledge on beta-amyloid.
Gerstner and co-researchers have studied the insects regarding the genetics of sleep since 1997. He brought that research to WSU Spokane when he took a position here less than three years ago.
“Sleep is exhibited in all animals; we should be able to find in a simple animal what sleep is doing,” he said. “One of the things it’s doing is to help clean out the trash, so to speak.”
One thought is when a person has lots of beta-amyloid pieces binding and becoming aggregate from the day, a certain mechanism occurring during sleep helps offset that, according to Gerstner.
“Sleep is somehow — we’re not sure of the mechanism — helping clear some of these beta-amyloids, we think. We’re in the middle of it. We’re learning.”
Sleep also seems to be important for restoring the ability to have cognitive function, Gerstner added.
Mysteries remain in the scientific world about the impact of plaque occurring from the built-up beta amyloid in the spaces between nerve cells. People can have plaque in the brain but not progress to full-blown Alzheimer’s disease, Gerstner said.
More sleep studies could unlock understanding of the mechanisms that occur in the brain during slumber. Another universal is the response when people or animals go for long hours without sleep, Gerstner said.
“When you’re out all night, the next day you’re sleeping in making up for sleep lost,” he said. “One of the goals is for us to identify what are the mechanisms, the biological underpinnings, of that need to recover lost sleep.”