Lack of Insulin Linked to Alzheimer's
Discovery might lead to new treatments, researchers say
MONDAY, March 7, 2005 (HealthDayNews) -- Two potentially significant discoveries about insulin may shed new light on how Alzheimer's disease ravages the brain, and might one day lead to new treatments.
The first discovery is that insulin is produced in the brain; the second is that Alzheimer's patients have impaired insulin production in their brains.
"Insulin is made in the brain. Previously it was thought to be made only in the pancreas," said lead researcher Dr. Suzanne de la Monte, an associate professor of pathology and medicine at Brown University. "In Alzheimer's disease, the production of insulin in the brain is substantially reduced."
In experiments with rats, de la Monte's team found insulin is produced in several areas of the brain. The researchers also discovered that reducing the production of insulin in the animals' brains added to the deterioration of brain cells, an early sign of Alzheimer's.
When de la Monte's team looked at brain tissue from deceased Alzheimer's patients, they found that insulin production was severely curtailed in areas of the brain affected by Alzheimer's.
"Moreover, in Alzheimer's disease, the insulin receptors -- the molecules that are important for receiving the signals from insulin -- are also reduced in the brain," de la Monte said.
Insulin is very important for maintaining brain cell function, de la Monte said. "If you don't have enough insulin or the ability to respond to insulin is impaired, then neurons will not function well and they probably will die," she explained.
To separate this form of insulin deficiency from diabetes, she has coined the term "type 3 diabetes."
"This is not diabetes as we know it," de la Monte added.
The findings appear in the March issue of the Journal of Alzheimer's Disease.
De la Monte believes the problems of insulin production in the brain start at the beginning of the disease process in Alzheimer's patients. "It starts early," she said. "Over time, it gets worse."
According to de la Monte, these discoveries might lead to new treatments for Alzheimer's. The therapies could involve either replacing insulin in the brain with some compound, or reactivating damaged insulin receptors. "If you are thinking about how to make the cells function better, you would be thinking about replacing what's missing or making the cells respond better than they do," she said.
In addition, de la Monte thinks the lack of insulin production in the brain may also play a role in other neurodegenerative diseases such as Parkinson's.
Dr. Samuel Gandy is vice chairman of the Alzheimer's Association's National Medical and Scientific Advisory Council.
He said that, while the suggestion of insulin's role in Alzheimer's is interesting, there are problems with the Brown study that make the link less than convincing.
Part of the problem is using brain tissue of deceased Alzheimer's patients, because that makes it impossible to tell at what point changes in the tissues occurred. "There are a lot of changes that are very late and very far down the pathogenetic stream, so it's hard to tell what's the chicken and what's the egg," Gandy said.
To determine whether changes in insulin production occur early in Alzheimer's, Gandy suggested the researchers would have to look at brain tissue of people newly diagnosed with Alzheimer's.
However, Gandy said there are some tantalizing clues in the Brown research that might lead to new approaches to the disease.
Another expert, William J. Netzer, a research associate at the Fisher Center for Alzheimer's Research Foundation at Rockefeller University in New York City, echoed Gandy's concerns.
"A considerable amount of research suggests a linkage between diabetes mellitus and Alzheimer's disease," Netzer said. "However, this linkage remains rather obscure."
Netzer also has problems with using brain tissue from late-stage Alzheimer's patients to study the origin of the disease. "The late-stage Alzheimer's disease brain has generally undergone catastrophic deterioration, and it is difficult to know whether observed changes are the cause of illness or a result of it," he said. "This is true even for changes that occur earlier. In fact, a lot is probably going on in the brain prior to development of the first symptoms of Alzheimer's disease."
"I think the link between insulin and glucose metabolism and Alzheimer's disease is well worth investigating, but I don't think the current paper adds very much to the debate," Netzer said.
Another study, from the March 8 issue of Neurology, finds that dementia is not a part of normal aging. Older men and women with mild cognitive impairment have either Alzheimer's disease or cerebral vascular disease, which can often lead to stroke, according to the report.
"The study shows that mild cognitive impairment is often the earliest clinical manifestation of one or both of two common age-related neurologic diseases," Dr. David A. Bennett, director of the Rush Alzheimer's Disease Center at Rush University Medical Center in Chicago, said in a prepared statement. "From a clinical standpoint, even mild loss of cognitive function in older people should not be viewed as normal, but as an indication of a disease process."
In their study, the researchers took brain tissue samples from 180 people. Thirty-seven had mild cognitive impairment, 60 did not have cognitive impairment, and 83 had dementia.
One positive finding was that 60 people whose average age was 85 did not have any cognitive decline after several years of follow-up. However, about half of these people had significant Alzheimer's disease and nearly a quarter had cerebral vascular disease. "It is likely that these individuals have some type of 'reserve' capacity in their brains that allows them to escape the loss of memory despite the accumulation of pathology," Bennett said.
"From a public health perspective, the number of people with cognitive loss due to Alzheimer's disease and cerebral vascular disease is probably much larger than current estimates," he said.
The Alzheimer's Association can tell you more about new research into the disease.