For years, researchers have been trying to find out what causes Alzheimer’s disease and how it is exacerbated in the hopes that this knowledge could lead to better treatments or a cure, or maybe even a method of preventing people from developing the disease in the first place. Now a group of researchers believes they’ve discovered a reason why amyloid plaque buildup is capable of causing Alzheimer’s disease, leading to a new avenue for treatments.
Scientists at the University of Texas at Dallas have just conducted a proof-of-concept study which yielded very promising results regarding the “hunger hormone” and its interactions with the amyloid protein fragments that have long been believed to cause memory loss in Alzheimer’s patients.
The “hunger hormone” is a hormone called ghrelin that is produced mainly in the stomach, although some of it is also made in the small intestine, pancreas, and brain. It serves to increase your appetite, stimulate you to eat, and promote fat storage, but it’s also known to be involved in memory preservation as well.
Ghrelin circulates through the bloodstream to the hippocampus and binds to ghrelin receptors. Then those activated receptors work together with activated dopamine receptors to form a protein complex that aids in the communication between brain cells and promotes memory.
However, these ghrelin receptors are easily blocked by amyloid-beta, which binds to the receptors and keeps ghrelin from binding in the proper place. Without the ghrelin, the receptors can’t form a protein complex, and neural communication begins to break down.
The hippocampus is among the first parts of the brain to be affected by Alzheimer’s disease, likely because of this phenomenon, and its importance in learning and memory makes it a particularly devastating part of the brain to lose function in.
“As the brain loses the function of ghrelin receptors due to amyloid-beta, the body tries to compensate by increasing the production of ghrelin and the number of ghrelin receptors,” says Dr. Heng Du, associate professor of biological sciences at UT Dallas and corresponding author of the study. “But the amyloid prevents the receptors from functioning.”
Du explains that this isn’t a one-time event but rather spirals downhill continuously, with the body trying to compensate but amyloid-beta continuing to block each new receptor, causing further disconnection between neurons.
A recent clinical trial involving a ghrelin-activating compound called MK0677 failed miserably, but Du believes it’s because it wasn’t working in conjunction with a dopamine-activating compound. In their new study, they treated mice with Alzheimer’s disease with both MK0677 and a compound called SKF81297 to activate both receptors at the same time.
“When we gave these compounds simultaneously, we saw improved cognition and memory in the AD mice, and lesions in the hippocampus were reduced,” Du said. “Activating both receptors at the same time was key; it restored the receptors’ ability to form complexes. When this happens, we suspect the ghrelin receptor becomes protected and can no longer bind to amyloid-beta. More research is needed, but targeting this mechanism might prove therapeutically useful.”
Du believes that his research shows that Alzheimer’s is more than just a brain disease—it has a lot to do with hormones too. He has filed a patent on his idea and hopes to continue his research in human subjects in the future.
“As we age, we tend to experience changes in metabolism,” he says. “These affect the heart and the gastrointestinal system, but maybe they also are affecting the brain by altering the ghrelin receptor. We know that even in the absence of dementia, many older people have memory problems, and this could be related to the dissociation between the receptors in the brain, even without the presence of amyloid. I’m starting to think of Alzheimer’s as a systemic disorder, and that we should pay more attention to the metabolic and hormonal path of the disease.”
Do you think Du could be on the right path? Only time and research will tell.Whizzco