In recent years, it became clear that people with diabetes face an ominous prospect — a far greater risk of developing Alzheimer’s disease. Biology Professor Chris Li and her colleagues at The City College of New York 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. 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 they found was that mutations in the worm-equivalent of the APP gene slowed their development, which suggested that some metabolic pathway was disrupted and then they began to examine how the worm-equivalent of APP modulated different metabolic pathways and 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 that when you knock out the worm-equivalent of APP, the animals die, they found. This tells 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.