Alzheimer's and Lack of Insulin Linked
< March 9, 2005 > -- Two potentially significant discoveries about insulin that may shed new light on how Alzheimer's disease ravages the brain, and that might one day lead to new treatments, have been reported in the Journal of Alzheimer's Disease.
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, Dr. 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 Dr. 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," Dr. de la Monte said.
Insulin is very important for maintaining brain cell function, Dr. 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," Dr. de la Monte added.
Dr. 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 Dr. 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, Dr. 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.
In an accompanying review article, Dr. de la Monte and accompanying author Dr. Jack Wands, of Rhode Island Hospital and Brown Medical School, write that "there is a genuine need for a 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."
Dr. Samuel Gandy, vice chairman of the Alzheimer's Association's National Medical and Scientific Advisory Council, says 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, PhD, 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, reported in 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.
Always consult your physician for more information.
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Alzheimer's disease is a progressive, neurodegenerative disease that occurs in the brain and often results in the following:
- impaired memory, thinking, and behavior
- confusion
- restlessness
- personality and behavior changes
- impaired judgment
- impaired communication
- inability to follow directions
- language deterioration
- impaired visiospatial skills
- emotional apathy
With Alzheimer's disease, motor function is often preserved.
When Alzheimer's was first identified by German physician, Alois Alzheimer, in 1906, it was considered a rare disorder. Today, with one in 10 persons over age 65 (and nearly half of persons over age 85) affected, Alzheimer's disease is recognized as the most common cause of dementia (a disorder in which mental functions deteriorate and breakdown).
Alzheimer's disease is distinguished from other forms of dementia by characteristic changes in the brain that are visible only upon microscopic examination during autopsy. Brains affected by Alzheimer's disease often show presence of the following:
- fiber tangles within nerve cells (neurofibrillary tangles)
- clusters of degenerating nerve endings (neuritic plaques)
Another characteristic of Alzheimer's disease is the reduced production of certain brain chemicals necessary for communication between nerve cells, especially acetylcholine, as well as norepinephrine, serotonin, and somatostatin.
Although intense investigation has been underway for many years, the causes of Alzheimer's disease are not entirely known. Suspected causes often include the following:
- age and family history
- certain genes
- abnormal protein deposits in the brain
- other risk and environmental factors
According to the Alzheimer's Association, the following are the most common symptoms of Alzheimer's disease. However, each individual may experience symptoms differently. Symptoms may include:
- memory loss that affects job skills
- difficulty performing familiar tasks
- problems with language
- disorientation to time and place
- poor or decreased judgment
- problems with abstract thinking
- misplacing things
- changes in mood or behavior
- changes in personality
- loss of initiative
The symptoms of Alzheimer's disease may resemble other medical conditions or problems. Always consult your physician for a diagnosis.
There is not a single, comprehensive test for diagnosing Alzheimer's disease. By ruling out other conditions through a process of elimination, physicians, or other specialists, can obtain a diagnosis of probable Alzheimer's disease with approximately 90 percent accuracy. However, the only way to confirm a diagnosis of Alzheimer's disease is through autopsy.
Always consult your physician for more information.
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