Scientists have discovered evidence suggesting that resistance to the “hunger hormone” ghrelin in the brain is linked to the cognitive impairments and memory loss associated with Alzheimer’s disease (AD).
Through observations of postmortem brain-tissue samples from Alzheimer’s patients and experiments with a mouse model of AD, the scientists looked into the relationship between ghrelin and learning and memory abilities. A possible treatment strategy for the incurable neurodegenerative disorder that affects about 5.8 million older adults in the U.S. was also suggested.
Ghrelin
Ghrelin, also known as the hunger hormone, is produced in the stomach and sends signals to the brain to regulate energy balance and body weight. It is usually linked to appetite and meal initiation, but is also implicated in learning and memory.
Ghrelin normally binds with ghrelin receptors, a protein in hippocampus, which combine with similarly activated receptors for the neurotransmitter dopamine. The two receptors then form a protein complex that helps maintain communication between brain cells which perform as the foundation of memory.
When a toxic buildup of protein fragments called amyloid beta binds to ghrelin receptors, however, the ability of ghrelin receptors to combine with dopamine receptors is blocked, causing cell death and damage in Alzheimer’s disease.
"Our hypothesis is that this dissociation between ghrelin and dopamine receptors may be what is affecting cognition in Alzheimer's patients," Dr. Heng Du, corresponding author of the study, said. "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. But the amyloid prevents the receptors from functioning."
Proof of the hypothesis
The hypothesis is proved by observations in insulin production in patients of type 2 diabetes. The body produces more insulin to bind insulin receptors in the early stage of type 2 diabetes, but the insulin receptors are unable to be activated. Similarly, ghrelin receptors cannot be activated in Alzheimer’s patients.
Du’s team also gave experiments in mice, proving that when provided with compounds to activate dopamine receptors, the mice showed improved cognition and memory, and reduced lesions in the hippocampus.
Further research is needed, but targeting the mechanism might prove therapeutically useful, said Du.
"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."
