Researchers at the University of Alabama at Birmingham found that long-term administration of a drug that mimics the hormone ghrelin protected Alzheimer's disease-model mice from memory deterioration, despite a high-glycemic-index (GI) diet.
In previous research, Inga Kadish and colleagues had shown that long-term (four months) administration of the ghrelin agonist - an experimental drug from Eli Lilly and Company that binds to the ghrelin receptor and produces an even greater response than ghrelin - protected Alzheimer's disease-model mice from memory deterioration.
"With chronic diseases like diabetes and Alzheimer's, you need to do a long-term study," said Kadish, an assistant professor in the Department of Cell, Developmental and Integrative Biology, UAB School of Medicine.
"So we did the long-term experiment with the worst-case scenario, a high-GI diet. Alzheimer's disease has 10 or 20 risk factors, and some of the strongest risk factors are diabetes or metabolic syndrome," Kadish said.
In contrast to short-term administration of the ghrelin agonist drug - which impairs insulin sensitivity and glucose tolerance, which are signs of metabolic syndrome and diabetes - the researchers found that the long-term ghrelin agonist treatment did not impair insulin signalling and glucose tolerance in Alzheimer's disease mice fed a high GI diet.
The test mice also showed more activity and reduced body weight and fat mass. The test mice also showed a beneficial impact of the long-term ghrelin agonist treatment on insulin signalling pathways in hippocampal brain tissue.
Alzheimer's patients show significant shrinkage of the hippocampus, a part of the brain cortex that has a key role in forming new memories.
"The present results suggest that ghrelin might improve cognition in Alzheimer's disease via a central nervous system mechanism involving insulin signalling," researchers said in the study published in the journal Scientific Reports.
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