In discovering a new form of diabetes, Brown re-searchers have also found a link between reduced insulin levels in the brain and the subsequent development of Alzheimer's disease. Professor of Pathology Suzanne de la Monte and colleagues have identified a Type 3 diabetes in the brain, a neuroendocrine disease completely distinct from Type 1 and Type 2.
De la Monte's study yielded two separate and significant findings. "We have been able to prove, for the first time, that insulin and its growth factors are produced in the brain, not just in the pancreas, as previously thought," she says. "And we have found that in people with Alzheimer's disease, the amount of insulin in the brain is markedly reduced, and insulin receptor cells are also reduced," which means the brain cells that normally respond to insulin have died. The result is insulin resistance, a kind of "brain diabetes" that precedes, and may cause, Alzheimer's-type changes in the brain, she says.
Interestingly, de la Monte stumbled across the insulin-Alzheimer's connection while studying alcohol's effect on the brain. "One of the things alcohol abuse does to the brain is to impact insulin," she says. " We were seeing brain degeneration and plaques caused by alcohol-related insulin resistance, and they looked just like the kind of damage caused by Alzheimer's disease." That observation led her to study the role insulin might play in Alzheimer's.
Type 1 and Type 2 diabetics needn't worry, de la Monte says. "This is not an obesity or a pancreas problem," she stresses. "We are talking about two separate things, even if the biochemical and molecular events are related."
Similarly, there is no indication that current diabetes treatments will cure or prevent Alzheimer's - at least not in the near future. Although current treatments have made diabetes a manageable disease, getting drugs to cross the blood-brain barrier is a significant challenge.
The Alzheimer's-insulin study involved looking at postmortem brain tissue at the molecular level, using technology and methods just five years old. Several Brown undergrads assisted on the study, including bioengineering concentrator Eric Steen '05, who was listed as first author on one of two papers the team published in the March Journal of Alzheimer's Disease. For three years, he has worked in the lab, studying insulin signaling pathways in normal and Alzheimer's diseased brains.
Lori Baker teaches fiction writing at Brown.