Could Alzheimer's Be a Form of Type 3 Diabetes?

In a report in the November issue of Journal of Alzheimer's Disease, a recent study shows that as insulin production in the brain decreases, Alzheimer's progresses. The finding that the brain produces insulin is recent, and it has been found that insulin levels in the brain and related cellular receptors fall precipitously during the initial phases of Alzheimer's. The insulin levels continue to drop progressively as the illness becomes more severe, which adds to the evidence that Alzheimer's might be a new form of diabetes. In addition, it was discovered that acetylcholine levels, something characteristic of Alzheimer's, are directly related to this insulin loss and the insulin-like growth factor function in the brain.

"Insulin disappears prematurely and dramatically in Alzheimer's disease," said senior researcher Suzanne M. de la Monte, neuropathology at Rhode Island Hospital and pathology professor at Brown University Medical School. Adding, "many of the unexplained characteristics of Alzheimer's seem to be related to abnormalities caused by insulin. This demonstrates that the disease is similar to a neuroendocrine disorder or another type of diabetes."

In their study, the researchers conducted an autopsy on the brain tissue of 45 patients who had been diagnosed with different degrees of Alzheimer's and compared the tissue with samples taken from individuals with no history of the disease. They also studied the insulin receptor function in the brain's frontal cortex, one of the areas most affected by Alzheimer's. This confirmed that as the Alzheimer's severity increased, the insulin receptor levels and the brain's ability to respond decreased.

The findings show two insulin-related abnormalities in Alzheimer's. First, the insulin levels decrease as the disease progresses. Second, insulin and its related protein, insulin-related growth factor-1, lose the ability to bind to the cell receptors. This creates a resistance to the insulin growth factors, causing cellular malfunctioning and death.

"We can show that insulin alteration occurs in the disease's initial phases and that it is related to neurotransmitters responsible for cognition. In addition, we can prove the relationship with abnormalities characteristic of Alzheimer's in the advanced stage. This work ties the concepts showing that Alzheimer's disease can be considered a Type 3 diabetes," La Monte said.

From observational studies "we have increasing evidence that diabetes, its predecessor metabolic syndrome and insulin resistance are implicated in increasing the risk for Alzheimer's disease," said Dr. Hugh C. Hendrie, who is professor and co-director at the Center for Alzheimer's disease and Related Neuropsychiatry Disorders at Indiana University Center for Aging Research in Indianapolis.

"There are many other factors also implicated in Alzheimer's Disease, such as hypertension

and inflammation, but it would be a bit of a stretch at the moment to confirm that Alzheimer's Disease is an endocrinological disorder similar to diabetes," he emphasized. If this were true, it might be possible for insulin treatments for diabetics to help slow down the progression of Alzheimer's. Evidence of this would be the results from Ishii's group treating rats with insulin-like growth factors and finding that the intervention prevented learning and memory loss.

"The clinical potential is that by injecting patients with insulin-like growth factors, one might be able to prevent learning and memory loss," Ishii said. "In particular, we have a paper about to published that shows that insulin-like growth factors not only prevent learning and memory loss, but also prevent the loss of a protein in the brain. This might lead to the slowing down of the progression of Alzheimer's."

SOURCES: Hugh C. Hendrie, M.B., Ch.B., D.Sc., professor, psychiatry, co-director, Center for Alzheimer's Disease and Related Neuropsychiatric Disorders, Indiana University Center for Aging Research, Indianapolis; Douglas N. Ishii, Ph.D., professor, Department of Biomedical Sciences, Colorado State University, Fort Collins; November 2005 Journal of Alzheimer's Disease.