"What we found is that insulin is not just produced in the pancreas, but also in the brain. And we discovered that insulin and its growth factors, which are necessary for the survival of brain cells, contribute to the progression of Alzheimer's," says senior author Suzanne M. de la Monte, a neuropathologist at Rhode Island Hospital and a professor of pathology at Brown Medical School. "This raises the possibility of a Type 3 diabetes."
It has previously been known that insulin resistance, a characteristic of diabetes, is tied to neurodegeneration. While scientists have suspected a link between diabetes and Alzheimer's disease, this is the first study to provide evidence of that connection.
By studying a gene abnormality in rats that blocks insulin signaling in the brain, researchers found that insulin and IGF I and II are all expressed in neurons in several regions in the brain.
Additionally, researchers determined that a drop in insulin production in the brain contributes to the degeneration of brain cells, an early symptom of Alzheimer's. "These abnormalities do not correspond to Type 1 or Type 2 diabetes, but reflect a different and more complex disease process that originates in the CNS (central nervous system)," the paper states.
By looking at postmortem brain tissue from people diagnosed with Alzheimer's disease, researchers discovered that growth factors are not produced at normal levels in the hippocampus – the part of the brain responsible for memory. The absence of these growth factors, in turn, causes cells in other parts of the brain to die. Reserachers found that insulin and IGF I were significantly reduced in the frontal cortex, hippocampus and hypothalamus – all areas that are affected by the progression of Alzheimer's. Conversely, in the cerebellum, which is generally not affected by Alzheimer's, scientists did not see the same drop in insulin and IGF I.
"Now that scientists have pinpointed insulin and its growth factors as contributors to Alzheimer's, this opens the way for targeted treatment to the brain and changes the way we view Alzheimer's disease," de la Monte says.
In an accompanying review article, de la Monte and accompanying author Jack Wands, MD, of Rhode Island Hospital and Brown Medical School, write that "there is a genuine need for thorough and comprehensive study of the neuropathological changes associated with diabetes mellitus, in the presence or absence of superimposed Alzheimer's Disease or vascular dementia."
The study was supported by grants from the National Institute of Alcoholism and Alcohol Abuse and from a COBRE award from the National Institutes of Health.
Founded in 1863, Rhode Island Hospital (www.rhodeislandhospital.org) is a private, not-for-profit hospital and is the largest teaching hospital of Brown Medical School. A major trauma center for southeastern New England, the hospital is dedicated to being on the cutting edge of medicine and research. Rhode Island Hospital ranks 13th among independent hospitals who receive funding from the National Institutes of Health, with research awards of more than $27 million annually. Many of its physicians are recognized as leaders in their respective fields of oncology, cardiology, orthopedics and minimally invasive surgery. The hospital's pediatrics wing, Hasbro Children's Hospital, has pioneered numerous procedures and is at the forefront of fetal surgery, orthopedics and pediatric neurosurgery.