Posted 12/15/2007 9:33 AM (GMT -7)
Hope I'm not violating any copyright. The folowing is from an e-mail service from John Hopkins. Mary
Memory Special Report
The Role of Insulin in the Development of Alzheimer’s Disease
Recent research suggests that a failure in insulin processing in the brain may contribute to the development of Alzheimer’s disease. Dr. Sam Grandy, Chair of the Medical and Scientific Advisory Council of the Alzheimer’s Association, talks about this intriguing new insight.
Researchers are getting closer to understanding how Alzheimer’s disease develops, and a key component in several emerging theories is insulin and its role in the brain. One reason uncovering the role of insulin in Alzheimer’s disease is so exciting is because drugs already exist to treat insulin deficiency in diabetes. These drugs might be used “as is” to treat Alzheimer’s disease, but even if they aren’t, they give researchers a head start.
Insulin does the important job of guiding the entry of glucose, the body’s main energy source, into cells. When insulin is deficient or the body fails to respond to it, as is the case with diabetes, small blood vessels are damaged from the excess glucose present in the bloodstream, and cells are damaged because they are cut off from their fuel supply.
Glucose is so important to brain cells that they don’t need insulin to absorb sugar. But some brain cells have insulin receptors and require insulin to spur them into action. Sam Gandy, M.D., Ph.D., Director, Farber Institute for Neurosciences at Thomas Jefferson University and Chair, Medical and Scientific Advisory Council of the Alzheimer’s Association, explains, “The role of insulin in the brain is different from its role in the rest of the body. In the brain, insulin helps nerve cells communicate. Insulin acts as the ‘accelerator’ on the nerve cell, revving up cell metabolism.”
It has been suggested that a failure in insulin processing in the brain may contribute to the development of Alzheimer’s disease. Dr. Gandy is quick to point out that Alzheimer’s disease is not a form of diabetes. The important distinction between what insulin does in the brain and what insulin does in the rest of the body underscores the finding, made by researchers at Rhode Island Hospital (RIH), that deterioration caused by insulin dysfunction in the brain is independent of whether a person has type 1 or type 2 diabetes.
RIH researchers compared brain tissue from 45 people who died in various stages of Alzheimer’s disease with brain tissue from people with no history of Alzheimer’s disease and found that insulin levels fell in the early stages of Alzheimer’s disease and continued to fall as the disease progressed. In the most advanced stages of Alzheimer’s disease, the cell receptors that process insulin were functioning at an 80% lower capacity than the receptors in healthy brain tissue.
In a 2005 study reported in the Journal of Alzheimer’s Disease, the same researchers injected the brains of rats with streptozotocin, a chemical compound that impairs insulin production. Examination revealed the characteristic signs of Alzheimer’s disease in the rats’ brains, including amyloid plaques, low levels of the neurotransmitter acetylcholine, and abnormal tau protein formation.
It has long been known that positron emission tomography (PET) scans of the brains of people with Alzheimer’s show a dramatic decrease in sugar utilization. Says Dr. Gandy, “In people who are at risk for Alzheimer’s disease, somewhere along the road to developing dementia, their sugar utilization changes. What’s not known is whether sugar utilization changes before or after people develop the symptoms of dementia and the structural changes such as beta-amyloid plaques.”
The National Institutes of Health is currently enrolling participants in The Alzheimer’s Disease Neuroimaging Initiative (ADNI) to “try to establish the temporal sequence of brain changes in people with Alzheimer’s,” continues Dr. Gandy. In addition to charting insulin changes, very sensitive neuroimaging tests are measuring minute structural changes, which may mark an early stage of clinical dementia.
On the horizon -- “Now that we think we understand how Alzheimer’s disease begins,” says Dr. Gandy, “the challenge is to find out when it begins and when we would have to start treating it to have effect. More research needs to be done and then we can begin the extended process of developing compounds that work first in test tubes, then in animals, and then in people.”
The theory that problems with insulin develop before structural changes in the brain and symptoms of dementia take place is already being put to the test with thiazolidinediones (TZDs), drugs used to treat type 2 diabetes. These drugs, which include Avandia (rosiglitazone) and Actos (pioglitazone), do the job of insulin when insulin can’t.
Recent studies with rosiglitazone suggest that, in addition to helping the body metabolize glucose, TZDs help normalize the brain cell signals that require insulin. Researchers at RIH have tested TZDs and similar compounds in rats injected with streptozotocin and found similar effects. In fact, many of the abnormalities associated with Alzheimer’s disease were reduced after treatment.
Studies also are following people taking TZDs to treat their type 2 diabetes to see if the drugs have any influence over the risk of developing Alzheimer’s disease. One study following 142,328 veterans with diabetes found 20% fewer new cases of Alzheimer’s disease among those treated with TZDs compared with veterans taking insulin or other types of diabetes drugs.
The ADNI will finish enrollment in the next few months and begin monitoring participants periodically for a 3- to 5-year period -- possibly longer. “It’s the largest systematic and organized approach to the question of what happens first that’s ever been taken,” says Dr. Gandy. In the past, studies have followed people with dementia. “We’ll be looking at people with and without dementia, between the ages of 70 and 90, over their lifespan, to see what happens along the road from aging to mild cognitive impairment to Alzheimer’s disease. Knowing what happens first,” Dr. Gandy states, “is the key to Alzheimer’s disease prevention.”
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