Possible Link Between Alzheimer's Disease And Diabetes
June 15, 2012

Possible Link Between Alzheimer’s Disease And Diabetes

Connie K. Ho for redOrbit.com

W. H. Auden once said, “There is more than meets the idea.” This idea can be applied to many things, but certainly in the realm of health and science. Connections that my have not seemed likely beforehand may appear as viable links through research. In particular, scientists from City College of New York-City University of New York (CCNY-CUNY) recently published research that shows a connection between Alzheimer´s disease and diabetes. The discovery could potentially lead to a therapeutic target for the two diseases.

Based on the scientists´ work, the findings show that people who have diabetes have a greater chance of developing Alzheimer´s disease. The study by CCNY-CUNY shows how there is a single gene that creates a relationship between the two diseases. The gene influences the insulin pathway and a tell-tale sign of diabetes is the disruption of that particular pathway.

"People with type 2 diabetes have an increased risk of dementia. The insulin pathways are involved in many metabolic processes, including helping to keep the nervous system healthy," remarked Professor Chris Li, a researcher at the Department of Biology at CCNY-CUNY, in a prepared statement.

The report, published in the June 2012 issue of the journal Genetics, describes how a gene in the worm Caenorhabditis elegan was found in multiple metabolic pathways like the insulin pathway; the gene in the worm is similar to a human gene related to Alzheimer´s disease.

"Mutations in three genes, including the amyloid precursor protein (APP) gene, have been correlated with the inherited form of Alzheimer's disease in humans," explained Li. "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.”

In the project, scientists examined worms with mutations in the Alzheimer´s-related gene (APL-1) as well as mutations in genes in the insulin pathway. They discovered that the Alzheimer´s-related gene affected metabolic pathways when the worms were developing. They also discovered that mutations in the Alzheimer´s-like gene created many changes in the worm´s common pathway, while mutations in the insulin pathway reversed those changes. A diagnosis of the disease after death is the appearance of plaques of amyloid protein in parts of patients´ brains.

"What we found was that mutations in the worm-equivalent of the APP gene slowed their development, which suggested that some metabolic pathway was disrupted," commented Li.

This finding demonstrates how the genes are linked to one another in a common pathway and explains a possible link between Alzheimer´s and diabetes; it also shows the importance of APL-1.

"When you knock out the worm-equivalent of APP, the animals die," stated Li. "This tells us that the APP family of proteins is essential in worms, as they are essential in mammals.”

The investigators hope that the results will help researchers focus on ways to develop new therapies for Alzheimer´s disease and diabetes. Much of the pharmaceutical industry has focused on treatments that work against the production and accumulation of amyloid plaques.

"Unfortunately, these efforts have not produced effective therapies yet, since the exact mechanisms of [Alzheimer´s Disease] are largely unknown. Given that the onset of [Alzheimer´s Disease] most likely results from the interaction of genetic and environmental factors, the research agenda should consider new platforms of study, going beyond the monolithic outlook of [Alzheimer´s Disease], by synthesizing epidemiological, experimental, and biological data under a unique pathophysiological model as a point of reference for further advances in the field,” commented Professor Vincenza Frisardi of the Department of Neurological and Psychiatric Sciences at the University of Bari in a prepared statement.

As such, each intersection in the Alzheimer´s-to-diabetes chain can be a possible target for drugs and treatment; Li plans to continue mapping crossroads in the pathway.

"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," noted Dr. Mark Johnston, Editor-in-Chief of Genetics, in the statement. "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."