[PHNUTR-L] Further evidence that Alzheimer's is a type of diabetes

[Kathrynne Holden, MS, RD]

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Public release date: 30-Nov-2005
http://www.eurekalert.org/pub_releases/2005-11/l-ild111705.php

Contact: Nicole Gustin
ngustin at lifespan.org
401-444-7299
Lifespan

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 
Providence, RI.

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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