Jun 14, 2012

Are Diabetes and Alzheimer's Linked?

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.

People with type 2 diabetes have an increased risk of dementia
A C. elegans worm with green
fluorescent protein (GFP) highlighting the
APL-1 Alzheimer-related protein in its body.
(Credit: Collin Ewald.)

From Alzheimer's Reading Room

Yesterday I published the details about a Phase 2 clinical trial for Alzheimer's and insulin -- Study of Nasal Insulin to Fight Forgetfulness.

If you go to the search box on the right hand side of this page and enter the word insulin, you will a long list of articles about Alzheimer's, diabetes, and insulin.

There are more than 5,000 articles in our Alzheimer's Reading Room knowledge base.

If you are looking for information, use the search box on the right. If you have not done so before try entering the word communication, or Alzheimer's World, you might be surprised to find how much information, useful information, we have here.

Today I was reading this new research summary from The City College of New York. I thought you might find it of interest. You might want to share this also.

Gene May Link Diabetes and Alzheimer’s

In recent years it became clear that people with diabetes face an ominous prospect – a far greater risk of developing Alzheimer’s disease. Now researchers at The City College of New York (CCNY) have shed light on one reason why. Biology Professor Chris Li and her colleagues have discovered that a single gene forms a common link between the two diseases.

They found that the gene, known to be present in many Alzheimer’s disease cases, affects the insulin pathway. Disruption of this pathway is a hallmark of diabetes. The finding could point to a therapeutic target for both diseases. The researchers report their finding in the June 2012 issue of the journal Genetics.
"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," said Professor Li, explaining why the link is not far-fetched.
Although the cause of Alzheimer’s is still unclear, one criterion for diagnosis of the disease after death is the presence of sticky plaques of amyloid protein in decimated portions of patients’ brains.

Mutations in the human "amyloid precursor protein" (APP) gene, or in genes that process APP, show up in cases of Alzheimer’s that run in families. In the study, Professor Li and her colleagues scrutinized a protein called APL-1, made by a gene in the worm Caenorhabditis elegans (C. elegans ) that happens to be a perfect stand-in for the human Alzheimer’s disease gene.

"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," said Professor Li. "We began to examine how the worm-equivalent of APP modulated different metabolic pathways and found that the APP equivalent inhibited the insulin pathway."

This suggested that the human version of the gene likely plays a role in both Alzheimer’s disease and diabetes.

They also found that additional mutations in the insulin pathway reversed the defects of the APP mutation. This helped explain how these genes are functionally linked.

The APL-1 is so important, they found, that “when you knock out the worm-equivalent of APP, the animals die," Li explained. “This tells us that the APP family of proteins is essential in worms, as they are essential in mammals,” like us.

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Professor Li and her colleagues 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 Dr. Mark Johnston, 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."
The research has identified one link in the chain, an Alzheimer's disease-related protein to the insulin pathway. This may provide insights into why type II diabetes patients are at higher risk for Alzheimer's. However, the protein fragments into many parts, each of which may attach to and signal neurons and other cells along the way. "The big question," said Professor Li, “Is how the amyloid precursor protein and its cleavage products intersect with the insulin pathway.”

Each intersection offers a possible target for drugs and other treatment. Professor Li plans to continue down the pathway, mapping its crossroads as she goes.

Professor Li conducted the research with then CUNY Graduate Center – City College graduate student, Collin Y. Ewald, and research assistant, Daniel A. Raps.

The research was funded by grants from the Alzheimer’s Association, the National Institutes of Health (NIH), the National Science Foundation (NSF), and a NIH Research Centers in Minority Institutions grant to The City College of New York.

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GENETICS a peer-reviewed, peer-edited journal of the Genetics Society of America (GSA), one of the world's most cited journals in genetics and heredity.

C. Y. Ewald, D. A. Raps, and C. Li. “APL-1, the Alzheimer’s Amyloid Precursor Protein in Caenorhabditis elegans, Modulates Multiple Metabolic Pathways Throughout Development,” Genetics, June 2012 Volume 191, Issue 2.

Original content Bob DeMarco, the Alzheimer's Reading Room