[PHNUTR-L] Insulin receptor stops progression of Alzheimer's disease

[Kathrynne Holden, MS, RD]

Colleagues, the following is FYI and does not necessarily reflect my own
opinion. I have no further knowledge of the topic. If you do not wish to
receive these posts, set your email filter to filter out any messages
coming from   @nutritionucanlivewith.com    and the program will remove
anything coming from me.
---------------------------------------------------------
Public release date: 21-Sep-2006
http://www.eurekalert.org/pub_releases/2006-09/l-irs092106.php

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

Insulin receptor stops progression of Alzheimer's disease

Patients could be treated in early phases of disease

Providence, RI – Stimulation of a receptor in the brain that controls 
insulin responses has been shown to halt or diminish the 
neurodegeneration of Alzheimer's disease, providing evidence that the 
disease can be treated in its early stages, according to a study by 
researchers at Rhode Island Hospital and Brown Medical School.

Researchers have found that peroxisome-proliferator activated receptor 
(PPAR) agonists prevent several components of neurodegeneration and 
preserve learning and memory in rats with induced Alzheimer's disease 
(AD). They found that an agonist for PPAR delta, a receptor that is 
abundant in the brain, had the most overall benefit.

"This raises the possibility that you can treat patients with mild 
cognitive impairment who have possible or probable Alzheimer's disease. 
This is really amazing because right now, there's just no treatment that 
works," says lead author Suzanne M. de la Monte, MD, MPH, a 
neuropathologist at Rhode Island Hospital and a professor of pathology 
and clinical neuroscience at Brown Medical School in Providence, RI.

The study appears in the September issue (Volume 10, Issue 1) of the 
Journal of Alzheimer's Disease (www.j-alz.com).

In previous studies, the researchers demonstrated that Alzheimer's is a 
brain-specific neuroendocrine disorder, or a Type 3 diabetes, distinct 
from other types of diabetes. They showed that insulin and IGF-I 
receptors are produced separately in the brain, and begin to disappear 
early in Alzheimer's and continue to decline as the disease progresses. 
As insulin signaling breaks down, it leads to increased oxidative 
stress, impaired metabolism and cell death – all causing neurodegeneration.

Scientists were also previously able to replicate Alzheimer's in rats 
with Streptozotocin (STZ), a compound that is known to destroy insulin 
producing cells in the pancreas and cause diabetes. When injected into 
the brains of rats, the compound mimicked the neurodegeneration of 
Alzheimer's disease – plaque deposits, neurofibrillary tangles, 
diminished brain size, impaired cognitive function, cell loss and 
overall brain deterioration.

Having created an animal model for Alzheimer's, researchers in this 
study induced Alzheimer's with STZ and then administered treatment with 
three classes of PPAR agonists – alpha, gamma and delta. All are found 
in various tissues and organs in the body, including the brain, and PPAR 
gamma is already FDA approved as a treatment for Type 2 diabetes, or 
adult-onset diabetes. The two other classes of PPAR agonists have not 
yet been approved for clinical use.

Following treatment, many of the abnormalities associated with 
Alzheimer's were reduced or nearly disappeared. The agonists affected 
different regions of the brain, with PPAR delta producing the most 
striking effect in preserving the hypothalamus and temporal lobes, areas 
of the brain responsible for memory, learning, and behavior. In these 
brain regions, PPAR alpha and PPAR gamma were effective in reducing 
amyloid gene expression. PPAR delta had the most benefit for reducing 
oxidative stress and improving learning and memory.

"That was the most spectacular," de la Monte says, "because everybody 
wants something for cognitive impairment, and that was the most improved 
with the PPAR delta agonist."

Researchers were not able to stop the deterioration of insulin and its 
receptors. However, by administering PPAR, they were able to bypass the 
defects in insulin signaling and preserve the cells that need insulin to 
thrive. PPAR molecules go directly to the nucleus of cells and tell DNA 
to turn on or off genes that are normally regulated by insulin, thus 
preventing them from dying and allowing them to communicate with each 
other. The major effects of the PPAR treatments were to increase brain 
size, preserve insulin and IGF-II receptor bearing neurons, and preserve 
learning and memory.

"The trigger for dementia is the loss of insulin and IGF producing 
cells. The cells that need those growth factors subsequently die. This 
study shows you can block the second phase, which is responsible for 
dementia. This is great news for patients since you treat early stages 
of disease," de la Monte says.

Another promising result for Alzheimer's patients is that these drugs 
could be given in the form of a pill, de la Monte says. In the study, 
the drugs were injected to control the amounts administered.

"One of the most exciting findings was that peripheral (intraperitoneal) 
injection of the PPAR agonists either partially or completely rescued 
the brains from neurodegeneration," the authors write.

Alzheimer's appears to be caused by parallel abnormalities – impaired 
insulin signaling and oxidative stress, which is regulated by the genes 
NOS and NOX. The PPAR agonists treatments target both problems. They 
preserve the cells regulated by insulin and IGF, and they decrease 
oxidative stress, resulting in fewer lesions in the brain.

"If the diagnosis is suspected or patients are in the early phases of 
AD, there's a good possibility they could get treatment that will help 
them. It's possible that in the moderate phase, treatment will also 
help, but more work needs to be done to show that," de la Monte says.

Treatment is not likely to work in the late stages of the disease, she 
says, because the cells have already died.
-- 
Kathrynne Holden, MS, RD < fivestar at nutritionucanlivewith.com >
"Ask the Parkinson Dietitian"  http://www.parkinson.org/
"Eat well, stay well with Parkinson's disease"
"Parkinson's disease: Guidelines for Medical Nutrition Therapy"
http://www.nutritionucanlivewith.com/