Alzheimer’s May Lead to Diabetes by Impairing Insulin Signaling in the Brain, New Research Finds
Patients with Alzheimer’s disease (AD) are more likely to develop diabetes due to an impairment in insulin signaling in the brain, according to a new study titled “Increased susceptibility to metabolic dysregulation in a mouse model of Alzheimer’s disease is associated with impaired hypothalamic insulin signaling and elevated BCAA levels,” published in the journal Alzheimer’s & Dementia.
In the past, epidemiological studies supported the hypothesis that diabetes patients have an enhanced risk of developing Alzheimer’s. But this new study, developed at the Icahn School of Medicine at Mount Sinai, shows the reverse may be happening.
Alzheimer’s disease is a debilitating, progressive neurodegenerative disorder, and the sixth-leading cause of death in the U.S. It gradually causes dementia in the elderly by reducing their memory and their ability to carry out daily activities. Diabetes, on the other hand, is a metabolic disease that, due to an insufficient insulin production, induces high blood sugar levels.
Icahn researchers have found that mouse models of Alzheimer’s disease develop insulin resistance in an area of the hypothalamus that regulates the metabolism of nutrients like amino acids, fatty acids, and glucose. The study also revealed that mice with Alzheimer’s had higher levels of branched chain amino acids (BCAA) in the blood, previously demonstrated to be regulated by insulin signaling in the brain. Although further confirmation in humans is still necessary, such findings suggest that BCAAs may be a biomarker for insulin action in the brain.
“This is the first study to suggest that Alzheimer’s disease pathology increases susceptibility to diabetes due to impaired insulin signaling in the hypothalamus,” said the study’s senior author, Christoph Buettner, M.D., Ph.D., associate professor of medicine, endocrinology, diabetes, bone disease, and neuroscience at the Icahn School of Medicine, in a press release.
The results will promote a re-evaluation of how these two diseases interact, and how to treat them. “Now that we have disease genes for dementia and diabetes, those genes are our ground zero, and the challenge is to work out all the steps and missteps between the gene and the patient and then to find interventions that cure those missteps,” said the study’s co-author, Sam Gandy, M.D., Ph.D.