A new spin to our understanding of the relationship between Alzheimer's disease and diabetes, which could point to a therapeutic target for both diseases, is published in a research report in the June 2012 issue of the journal Genetics. In the report, scientists from City College of New York-City University of New York (CCNY-CUNY) show that a gene in the worm Caenorhabditis elegans, which is similar to a human gene correlated with Alzheimer's disease, is involved in multiple metabolic pathways, including the insulin pathway.
"Mutations in three genes, including the amyloid precursor protein (APP) gene, have been correlated with the inherited form of Alzheimer's disease in humans," said Chris Li, Ph.D., a researcher involved in the work from the Department of Biology at CCNY-CUNY. "Because the equivalent gene we're studying in the model organism C. elegans is involved in many metabolic pathways, it suggests that the human version of the gene likely also plays a role -- not only in Alzheimer's disease, but in diabetes as well," Li added.
To make this discovery, these investigators studied worms with mutations in the Alzheimer's-related gene (APL-1) along with mutations in genes in the insulin pathway, and found that the Alzheimer's-related gene influenced metabolic pathways during the worms' development. They also found that, while mutations in the Alzheimer's-like gene caused severe disruptions in the worm's development, certain compensatory mutations in the insulin pathway reversed those defects. This discovery is important because it helps explain how these genes are functionally linked in a common pathway, and gives a possible explanation for the apparent link between Alzheimer's and diabetes in humans. Scientists hope that this new insight will help focus research in ways that might lead to new therapies in the treatment of both Alzheimer's disease and diabetes.
"This is an important discovery, especially as it comes on the heels of the U.S. government's new commitment to treat and prevent Alzheimer's disease by 2025," said Mark Johnston, Ph.D., Editor-in-Chief of Genetics. "We know there's a link between Alzheimer's and diabetes, but until now, it was somewhat of a mystery. This finding could open new doors for treating and preventing both diseases."
Rare variant analysis reveals genetic spectrum of monogenic diabetes genes