[PHNUTR-L] Further evidence that Alzheimer's is a type of diabetes
Kathrynne Holden, MS, RD
fivestar at nutritionucanlivewith.com
Thu Dec 1 08:10:59 PST 2005
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Public release date: 30-Nov-2005
Contact: Nicole Gustin
ngustin at lifespan.org
Insulin levels drop with progression of Alzheimer's disease, linked to
tangles in brain
Further evidence that Alzheimer's is a type of diabetes
Researchers at Rhode Island Hospital and Brown Medical School have
discovered that insulin and its receptors drop significantly in the
brain during the early stages of Alzheimer's disease, and that levels
decline progressively as the disease becomes more severe, leading to
further evidence that Alzheimer's is a new type of diabetes. They also
found that acetylcholine deficiency, a hallmark of the disease, is
linked directly to the loss of insulin and insulin-like growth factor
function in the brain.
The study, published in the November issue of the Journal of Alzheimer's
Disease (http://www.j-alz.com), is the first to look at insulin levels
early in the course of the disease. The authors' previous work published
earlier this year primarily focused on the late stages of Alzheimer's.
"Insulin disappears early and dramatically in Alzheimer's disease. And
many of the unexplained features of Alzheimer's, such as cell death and
tangles in the brain, appear to be linked to abnormalities in insulin
signaling. This demonstrates that the disease is most likely a
neuroendocrine disorder, or another type of diabetes," says senior
author Suzanne M. de la Monte, a neuropathologist at Rhode Island
Hospital and a professor of pathology at Brown Medical School in
The study analyzed postmortem brain tissue of 45 patients with a
diagnosis of either normal aging or different degrees of Alzheimer's
neurodegeneration, termed "Braak Stages." Researchers analyzed insulin
and insulin receptor function in the frontal cortex, a major area
affected by Alzheimer's. They found that with increasing severity of the
disease, levels of insulin receptors and the brain's ability to respond
to insulin decreased markedly.
"In the most advanced stage of Alzheimer's, insulin receptors were
nearly 80 percent lower than in a normal brain," de la Monte says.
Researchers found two parallel abnormalities related to insulin in
Alzheimer's. First, insulin levels decline as the disease progresses.
Second, insulin and its related protein IGF-I lose their ability to bind
to corresponding cell receptors, creating a resistance to the growth
factors and thus causing cells to malfunction and eventually die.
"This has important implications for treatment," de la Monte says. "If
you could target the disease early, you could prevent the further loss
of neurons. But you would have to target not just the loss of insulin
but the resistance of its receptors in the brain."
Researchers also offer an explanation for the acetylcholine deficiency
that is linked to dementia and has long been recognized as an early
abnormality in Alzheimer's. They found that insulin and IGF-I stimulate
the expression of choline acetyltransferase (ChAT), the enzyme
responsible for making acetylcholine. This discovery shows a direct link
between insulin and IGF-I deficiency and dementia.
"We're able to show that insulin impairment happens early in the
disease. We're able to show it's linked to major neurotransmitters
responsible for cognition. We're able to show it's linked to poor energy
metabolism, and it's linked to abnormalities that contribute to the
tangles characteristic of advanced Alzheimer's disease. This work ties
several concepts together, and demonstrates that Alzheimer's disease is
quite possibly a Type 3 diabetes," de la Monte says.
Earlier this year, de la Monte and co-authors provided the first
evidence that insulin and its related proteins are produced in the brain
and that reduced levels of both are linked to the late stages of
Alzheimer's. They surmised that Alzheimer's is a complex neuroendocrine
disease that originates in the central nervous system, raising the
possibility of a new type of diabetes.
Kathrynne Holden, MS, RD < fivestar at nutritionucanlivewith.com >
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"Parkinson's disease: Guidelines for Medical Nutrition Therapy"
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