Dementia & Diabetes: The Missing Link?

By Janice Wood Associate News Editor

People with diabetes face a far greater risk of developing Alzheimer’s disease and now researchers at The City College of New York say they have found a reason why.

Biologist Dr. Chris Li and her colleagues found that a single gene, known to be present in many Alzheimer’s disease cases, disrupts the insulin pathway, which is a hallmark of diabetes. The finding could point to a therapeutic solution for both diseases, the researchers say.

“People with type 2 diabetes have an increased risk of dementia,” said Li. “The insulin pathways are involved in many metabolic processes, including helping to keep the nervous system healthy.”

Although the cause of Alzheimer’s is still unknown, one criterion for diagnosis of the disease after death is the presence of sticky plaques of amyloid protein in decimated portions of patients’ brains, the researchers noted.

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, 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 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, she said.

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

She adds she hopes this new insight will help focus research in ways that might lead to new therapies in the treatment of both Alzheimer’s 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  the journal Genetics, which published the study.

“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.”

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