Gene may link diabetes and Alzheimer's, researchers find

June 14, 2012

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 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.

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 , but until now, it was somewhat of a mystery. This finding could open new doors for treating and preventing both diseases."

Professor Li has identified one link in the diabetes-to-Alzheimer's chain. However, the protein fragments into many parts along the insulin pathway, each of which may attach to and signal neurons and other cells along the way. "The big question," she said, "Is how the amyloid precursor protein and its cleavage products intersect."

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.

Explore further: Researchers identify how a gene linked to both Alzheimer's disease and type 2 diabetes works

More information: 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.

Related Stories

Researchers identify how a gene linked to both Alzheimer's disease and type 2 diabetes works

July 18, 2011
Researchers at Mount Sinai School of Medicine have identified how a gene for a protein that can cause Type 2 diabetes, also possibly kills nerve cells in the brain, thereby contributing to Alzheimer's disease.

Road block as a new strategy for the treatment of Alzheimer's

August 22, 2011
Blocking a transport pathway through the brain cells offers new prospects to prevent the development of Alzheimer's. Wim Annaert and colleagues of VIB and K.U. Leuven discovered that two main agents involved in the inception ...

Weight loss after gastric bypass surgery reduces expression of Alzheimer's genes

June 6, 2011
Obesity is a risk factor for Alzheimer's disease, but weight loss due to bariatric surgery may reduce the risk of this common dementia, a new study suggests. The results will be presented Sunday at The Endocrine Society's ...

Characterizing a toxic offender

December 9, 2011
The brains of individuals with Alzheimer's disease contain protein aggregates called plaques and tangles, which interfere with normal communication between nerve cells and cause progressive learning and memory deficits. Now, ...

Alzheimer's protein kills nerve cells in nose

September 27, 2011
A protein linked to Alzheimer's disease kills nerve cells that detect odors, according to an animal study in the September 28 issue of The Journal of Neuroscience. The findings shed light on why people with Alzheimer's disease ...

Recommended for you

A rogue gene is causing seizures in babies—here's how scientists wants to stop it

July 26, 2017
Two rare diseases caused by a malfunctioning gene that triggers seizures or involuntary movements in children as early as a few days old have left scientists searching for answers and better treatment options.

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.