Alzheimer's Could Be Diabetes-like Illness, Study Suggests

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Alzheimer's Could Be Diabetes-like Illness, Study Suggests

By Steven Reinberg

HealthDay Reporter on 11/30/2005

 

WEDNESDAY, Nov. 30 (HealthDay News) -- Could Alzheimer's be a form of

diabetes?

That's the tantalizing suggestion from a new study that finds insulin

production in the brain declines as Alzheimer's disease advances.

" Insulin disappears early and dramatically in Alzheimer's disease, " senior

researcher Suzanne M. de la Monte, a neuropathologist at Rhode Island Hospital

and a professor of pathology at Brown University Medical School, said in a

prepared statement.

" 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, " she added.

The discovery that the brain produces insulin at all is a recent one, and de

la Monte's group also found that brain insulin produced by patients with

Alzheimer's disease tends to fall below normal levels.

Now her group has discovered that brain levels of insulin and its related

cellular receptors fall precipitously during the early stages of Alzheimer's.

Insulin levels continue to drop progressively as the disease becomes more

severe -- adding to evidence that Alzheimer's might be a new form of diabetes,

she

said.

In addition, the Brown University team found that low levels of acetylcholine

-- a hallmark of Alzheimer's -- are directly linked to this loss of insulin

and insulin-like growth factor function in the brain.

The report appears in the November issue of the Journal of Alzheimer's

Disease.

In its study, de la Monte's team autopsied the brain tissue of 45 patients

diagnosed with different degrees of Alzheimer's called " Braak Stages. " They

compared those tissues to samples taken from individuals with no history of the

disease.

The team analyzed insulin and insulin receptor function in the frontal cortex

of the brain, a major area affected by Alzheimer's. They found that as the

severity of Alzheimer's increased, the levels of insulin receptors and the

brain's ability to respond to insulin decreased.

" In the most advanced stage of Alzheimer's, insulin receptors were nearly 80

percent lower than in a normal brain, " de la Monte said.

In addition, the researchers found two abnormalities related to insulin in

Alzheimer's. First, levels of insulin dropped as the disease progressed.

Second, insulin and its related protein -- insulin-related growth factor-I --

lose

the ability to bind to cell receptors. This creates a resistance to the

insulin growth factors, causing the cells to malfunction and die.

" We're able to show that insulin impairment happens early in the disease, " de

la Monte said. " 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, " she said.

One expert believes declining insulin levels may be an important feature of

Alzheimer's, but not the whole story.

" There is now increasing evidence primarily from observational studies that

diabetes, its predecessor metabolic syndrome, and insulin resistance are

implicated in increasing risk for Alzheimer's disease, " said Dr. Hugh C.

Hendrie.

He is a professor of psychiatry and co-director of the Center for

Alzheimer's Disease and Related Neuropsychiatric Disorders at Indiana University

Center

for Aging Research, in Indianapolis.

This study adds support to these biological hypotheses and has perhaps

treatment implications for the use of certain types of anti-diabetes drugs that

influence insulin resistance, Hendrie said.

" There are many other factors also implicated in Alzheimer's disease, such as

hypertension and inflammation, so I think it's a bit of a stretch at the

moment to describe Alzheimer's disease as an endocrinological disorder like

diabetes, " he said.

Another expert thinks that insulin and insulin-like growth factors may be the

key to slowing the progression of Alzheimer's.

" We have shown that insulin-like growth factors regulate learning and

memory, " said Douglas N. Ishii, a professor in the Department of Biomedical

Sciences at Colorado State University in Fort Collins. " We had shown that by

blocking insulin-like growth factors in the brain you block learning and

memory. "

When Ishii's group treated rats with insulin-like growth factors, the

researchers found that the intervention prevented the loss of both learning and

memory. " In addition, we showed that insulin normally regulates brain weight in

adults, " he said.

" The clinical potential is that by injecting insulin-like growth factors into

patients, one might be able to prevent the loss of learning and memory, "

Ishii said. " In particular, we have a paper coming out showing that

insulin-like

growth factors can not only prevent the loss of learning and memory, but

prevent the loss of a protein in the brain. This may lead to the slowing down

of

the progression of Alzheimer's. "