Wednesday, July 27, 2011


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.

Insulin Receptors

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.

Clinical Potential

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."

Read the full article here.

Wednesday, July 20, 2011


Here is today's blog post from neurosurgeon Dr. Jack Kruse, concerning the use of a low carb paleolithic diet to prevent Alzheimer's Disease, Parkinson's Disease and other neurodegenerative diseases:

Dr. Jack Krus

1. Why the presence of genes means nothing to disease risk.

2. What do people over 100 years old teach us about genetics?

3. What six pieces of evidence found in 2011 tell us about AD or PD etiology?

4. How will industry try to solve the mystery?

5. What you can do right now to obliterate your current risk of AD and PD?

If you did not know that Ronald Reagan suffered and died from end stage Alzheimer’s, you do now. Micheal J. Fox is afflicted with Parkinson’s disease and trying to solve its etiology as a fundraiser. Recently in 2011, several announcements were made that several genetic mutations seem to predispose us to Alzheimer’s disease (AD) and Parkinson’s Disease (PD). I tend to glance over these findings often because based upon my current understanding, genetic mutations are not where science seems to be headed these days. Genetic determinism has been the dogma for the last 50 years, but the most recent data suggest that we can reprogram our genes by turning on and off their function if we know how. This makes sense considering that most biologic systems don’t rely on the presence or absence of genes in disease states. In fact, in Mount Sinai’s supercentenarian group they found that the longest lived people all tend to have the “bad genes” in their cells we all worry about. The interesting part is that they are not “turned on” and appear to be of no consequence to those people.

The old dogma led us to believe that the mere presence of these genes spelled doom. If you don’t think genetic determinism is alive and wellin 2011 talk to any woman who tests positive for the BRCA 1 gene for breast cancer. Many of these women are electing for mastectomies in the face of no immediate cancer presence just because of the scare due to the BRCA 1 gene being present. I don’t advocate that kind of thinking. WHY? The Mount Sinai supercentenary group makes a great example for us to learn from. Think of an analogy of genes and their epigenetic signals to a “stick of dynamite” and “lit match”. A stick of dynamite is not dangerous to us unless it is around a lit match. It appears the same is true for genes. The mere presence means little as long as the on switch is not present at the same time. This is where genetic testing is now headed.

The recent AD announcements gained lots of attention but the thing that caught my eye about the genes found in AD patients were all tied to lipid metabolism and inflammation generation. The AD jigsaw puzzle is a long way from complete, but the pieces are emerging that suggests inflammation is the root cause of this condition. So Dr. Kruse, what exactly are those pieces of evidence? What six things have we learned about the brain and neurodegenerative disorders as of 2011?

1. The genesis cause of AD et al is caused by the presence of insoluble plaques made up of a protein called Amyloid beta (A-beta) inside neurons.

These proteins block signal transmission and molecule transfers that occur in the brain normally. This process continues for sometime and then another protein becomes more common called Tau protein. When both occur together they begin to interact and form the insoluble protein called a neurofibrillary tangle that is classically associated with many neurodegenerative diseases. (AD, Parkinson’s, and Mad Cow disease are a few.)

2. The second bit of evidence is found on the APO E gene present on chromosome 19. If it is present many researchers and clinicians believe your risk of getting AD rises. In fact, having two copies of the four we have of this gene, raises your risk of developing AD 20 fold before the age of 75! SO APO E presence sound bad does it not?

Guess what APO E gene function is for? It is to remove the build up of the A-beta and Tau proteins before they induce nerve damage and eventual cell suicide. The solubility factor is important because it is determined by how the protein folds after it is made. If it folds incorrectly it become less soluble. This is why we can see these tangles under a microscope. So this means that the presence of APO E gene is a great thing and not a bad thing that many have been led to believe the last 15 years. More proof that genetic determinism is not as important as the epigenomic effects upon those genes.

3. The third bit of evidence comes from Dr Chris Dobson’s lab in Cambridge University.

He cleverly made 17 small genetic adjustments to the A-beta protein in the lab to make it either more or less soluble. After doing this he then transferred these genetically altered proteins into the DNA of fruit flies and clearly proved that the less soluble the protein transferred the shorter lived were the flies. Their life spans clearly correlated with the percent solubility of the protein transferred to the mutant flies. So after his experiment neuroscientists began to ask why do misfolded proteins show up in elderly brains to begin with?

4. It appears that all neurons have an internal quality control mechanism that not only detects misfolded proteins, but one that also self corrects this process from happening.

Research was published in March of 2011 from Brown University that both parts of this mechanism, the detector and refolder, are functional but overwhelmed in diseased brains with neurodegenerative changes. They can not keep up with the workload of all the A- beta protein being made.

5. Then the 5th bit of evidence came in April of 2011 from Dr. Jeffrey Kelly.

Dr. Kelly is at the Scripps Research Institute, and found that a chemical formed when cholesterol reacts with ozone attaches to A-beta and makes misfolding hundreds of times more likely. Take a guess where Dr. Kelly found the ozone came from? It comes from inflammation generated within the neurons from cellular metabolism. This linked the etiology of protein misfolding directly to carbohydrate and omega six fuels in our diet and their eventual metabolism over years. Both of these pathways are known to cause the development of inflammation in human biochemistry. It also links diabetes risk to AD fairly tightly. This news is not surprising to my readers at all if you follow the Quilt’s Levees.

6. The last bit of evidence comes from the recent studies on studies on stress and the development of all neurodegenerative diseases. That is the hormone cortisol. This links another levee to the "brick in the wall".

This is a clearly a hormone most of my blog readers have become quite familiar with. Remember that cortisol rises in end stage leptin resistance to cause the generation of even more inflammatory cytokines. Remember that cortisol is made from the cholesterol backbone, pregnenolone. 2011 work done at the University of California at Irvine has pointed to the elevation of cortisol as the main generator of the inflammation in diseased neurons. This further fuels protein misfolding and overwhelms the detector and refolding mechanisms in the brain.


It appears that the brains cholesterol stores are used up to make the cortisol that fuels the inflammation that drives this pathologic process. This inflammation becomes the currency that overwhelms the internal quality assurance system of neurons to make sure proper protein folding occurs. When the system is overwhelmed the end result is the formation of neurofibrillary tangles from insoluble proteins. These insoluble proteins then block the transport of vital ingredients into the brain cells to offset the assault. One of those ingredients appears to be cholesterol itself. It appears that normal lipid metabolism repair mechanisms become so unbalanced that it induces the nerve cells to undergo apoptosis! This ties another levee to the AD and Parkinson’s disease story.

Many physicians and researchers are hoping that we can find a place in this chain of events that can be attacked or blocked by a medication to prevent the inflammation, production of ozone reactions, slow the conversion of cholesterol to cortisol, and encourage the refolding apparatus that evolution provided us to make a dent in this disease. Maybe then we can improve protein solubility and even boost the plaque removal mechanism that we were born with? I have a better idea. Why don’t we stop providing that the fuels that are known to provide the ” lit match” to the dynamite?

Maybe we should advocate a low carb paleolithic diet that decreases carbohydrates that upregulate IGF 1 and 2 and lower omega six free fatty acids? We know that will help slow the progression of the disease since we now know what drives it. Some how I bet they’d rather make a drug they could make money on then teach people what really might help now? After all, no food company makes money unless they are selling the SAD (Standard American Diet), do they? The choice is clearly yours to ponder.

To read the full article and comments, click here.