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TUESDAY, June 24, 2003 (HealthDayNews) -- Insulin might be involved in the build-up of protein plaques in the brains of people with Alzheimer's disease, according to a preliminary study.
If true, the finding might one day lead to new treatments to combat plaques in the brain, a hallmark of the disease.
"We looked at the effects of raising insulin on beta amyloid, the protein that collects in brains of patients with Alzheimer's disease," says Suzanne Craft, lead author of the study appearing in the June 24 issue of Neurology.
"We found that insulin increased levels of protein in the spinal fluid and, particularly, the older the participant was, the more likely the protein levels were increased," she says.
Although the study was a small one, involving only 16 people, there are some important implications, adds Craft, associate director at the geriatric research center at Veterans Affairs Puget Sound, in Seattle.
In the past several years, research has shown that people with any of several disorders characterized by high levels of insulin also have an increased risk for Alzheimer's disease. Those high-insulin disorders include type 2 diabetes, hypertension and metabolic syndrome.
"For some time there has been an association between diabetes and dementia, [but] we do not know the exact pathway by which such an association comes about," says Zaven Khachaturian, senior advisor to the Alzheimer's Association on medical and scientific affairs.
"If it can be established that it is a causal factor, then prevention measures or therapies that are being developed for these other disorders could also help Alzheimer's. But that needs to be proven. This is very preliminary," Khachaturian adds.
It's also known that people with Alzheimer's have a build-up of beta amyloid proteins in the brain, although it's not clear yet whether the proteins actually cause the illness. It is, however, considered a good possibility.
The reason: People with early onset Alzheimer's have gene mutations that lead to an increase in beta amyloid production -- in particular, the longer forms of the protein, such as beta amyloid 42, says Dr. Douglas Galasko. He's the author of an editorial in the same issue of Neurology, and a professor of neurosciences at the University of California, San Diego.
But what might explain the cause of early onset Alzheimer's may not explain the far more prevalent late-life version of the disease.
"One of the nagging questions is what does this have to do with late-life Alzheimer's disease, which really accounts for 95 percent or more of everybody we will see with Alzheimer's?" Galasko says. "We don't have clear evidence from anywhere that beta amyloid is overproduced in late-onset Alzheimer's."
If it's not overproduction that's the culprit, then it might be something else, possibly decreased breakdown or "clearance" of the protein, Craft and Galasko say.
Beta amyloid is created and broken down in healthy people all the time, although scientists aren't sure what its role is in the body. It's possible that the longer forms of the protein, such as amyloid 42, have no real function at all.
Craft and her colleagues focused specifically on the clearance -- the breaking down and purging -- of beta amyloid 42 from the brain to the spinal fluid in 16 healthy, older adults.
Ten women and six men each underwent, at separate times, two infusions either of a placebo or insulin plus dextrose, a sugar. Then they had their blood, spinal fluid and cognitive abilities measured.
Not surprisingly, the insulin infusion produced an increase in insulin concentration in the spinal fluid sample. More notably, it also led to an increase in amyloid 42, especially in older participants.
Interestingly, insulin infusion improved memory performance in the younger participants. But older participants who had an increase in beta amyloid 42 levels in their spinal fluid showed a decline in memory skills.
"It's possible that higher amyloid in their spinal fluid reflected a problem with clearing insulin in the brain," Craft suggests.
Galasko says it's unclear why the protein was found in the spinal fluid. One leading theory is that both insulin and beta amyloid 42 are competing for the attention of IDE, or insulin-degrading enzyme. This is one of the main enzymes that clear both beta amyloid and insulin. If IDE is showing a preference for insulin when both substances are present, then the beta amyloid will lose out, the theory goes.
Still, the new study is potentially significant, researchers agree. "It is the first demonstration in humans that levels of this protein can be affected by an acute challenge of any sort," Craft says.
Adds Galasko: "[Another] part of the study which is of interest is the general concept that we can do something, give some kind of substance [for example, insulin] that alters levels of beta amyloid in the spinal fluid and this has not been an easy thing to prove. At present, we don't have any available treatment for Alzheimer's disease that alters beta amyloid, so it's encouraging."
The findings could eventually open up a new class of therapies for Alzheimer's, experts say.
"What's happening is a bit of a paradigm shift within the field," Craft says. "Different areas within Alzheimer's disease that are now coming to the forefront have to do more with metabolic processes, with inflammation. We're looking at agents that reduce insulin levels. Insulin sensitizers that have been brought to use for diabetes in the past three to four years may actually benefit patients with Alzheimer's."
However, Khachaturian cautions, "drug development is a long, tedious process and many, many promising leads [get] derailed. We hope it doesn't happen here."
More information
For more on Alzheimer's disease, visit the Alzheimer's Association. For more on insulin and diabetes, visit the National Institute of Diabetes & Digestive & Kidney Diseases.
