Insulin resistance in the brain precedes and contributes to cognitive decline above and beyond other known causes of Alzheimer's disease, according to a new study by researchers from the Perelman School of Medicine at the University of Pennsylvania. Insulin is an important hormone in many bodily functions, including the health of brain cells. The team identified extensive abnormalities in the activity of two major signaling pathways for insulin and insulin-like growth factor in non-diabetic people with Alzheimer's disease. These pathways could be targeted with new or existing medicines to potentially help resensitize the brain to insulin and possibly slow down or even improve cognitive decline.
This is the first study to directly demonstrate that insulin resistance occurs in the brains of people with Alzheimer's disease. The study is now online in the Journal of Clinical Investigation.
"Our research clearly shows that the brain's ability to respond to insulin, which is important for normal brain function, is going offline at some point. Insulin in the brain not only modulates glucose uptake, but also promotes the health of brain cells - their growth, survival, remodeling, and normal functioning. We believe that brain insulin resistance may be an important contributor to the cognitive decline associated with Alzheimer's disease," said senior author, Steven E. Arnold, MD, professor of Psychiatry and Neurology. Arnold is also the director of the Penn Memory Center, a National Institute on Aging-designated Alzheimer's Disease Core Center. "If we can prevent brain insulin resistance from occurring, or re-sensitize brain cells to insulin with any of the currently available insulin-sensitizing diabetes medicines, we may be able to slow down, prevent, or perhaps even improve cognitive decline.
The risk of developing Alzheimer's disease is increased by 50 percent in people with diabetes. Type 2 diabetes is due to insulin resistance and accounts for 90 percent of all diabetes. The defining clinical feature of Type 2 diabetes (and Type 1 "juvenile" diabetes) is hyperglycemia - high levels of sugar in the blood - but there is no evidence that the brain in Alzheimer's is hyperglycemic. Insulin acts differently in the brain than in the rest of the body. Researchers found that insulin resistance of the brain occurs in Alzheimer's disease independent of whether someone has diabetes, by excluding people with a history of diabetes from this study.