Comments by J. C. Spencer

Beneficial sugars in the brain give the brain and body a long and healthy life. A shortage of these nutrients starve the brain, triggers Alzheimer�s, and causes slow death. Glycomics will continue to play the major role in correcting Alzheimer�s and other neurodegenerative diseases. I have contended for years that glycomics is the OS (Operating System) not only of the brain but every neuron and, in fact, every cell in the human body. Sugar is vital in every DNA strand of the body as the structural component in the DNA double helix backbone. This places sugars at the base of all data in your body. The two known �switch flippers� for altering gene expression are TOXINS or SUGARS.

If we are ever to address the healthcare crisis, we must focus on the cause and stop treating the symptom. Treating symptoms IS the cause for our healthcare crisis. When the OS is functioning properly, the data is conveyed correctly. Furthermore, instructions are given to repair altered gene expression and turn on or off the necessary cell functions. When your OS is not functioning properly the balance of everything can malfunction which causes the production of too much or too little of the enzymes and key proteins needed for the moment.

The subject of today�s article, Robert Vassar, discovered the enzyme that may be the cause for amyloid protein plaque build-up that causes Alzheimer�s. That is, when the communication system is not equipped with the necessary nutrients.

BACE1 is a protease responsible for the proteolytic processing of the amyloid precursor protein (APP). Amyloid beta peptide is the major constituent of amyloid plaques in the brains of individuals afflicted with Alzheimers disease. This peptide is generated from the beta-amyloid precursor protein (beta APP) in a two-step process. The first step involves cleavage of the extracellular, amino-terminal domain of beta APP. Protein cleavage is performed by an aspartyl protease termed beta-secretase (BACE), of which there are two isoforms, BACE1 and 2. This enzyme is synthesized as a propeptide that must be modified to the mature and active form by the prohormone convertase furin. Beta APP cleavage by the mature form of BACE results in the cellular secretion of a segment of beta APP and a membrane-bound remnant. This remnant is then processed by another protease termed gamma-secretase. Gamma-secretase cleaves an intra-membrane site in the carboxyl-terminal domain of beta APP, thus generating the amyloid beta peptide.

[The next four paragraphs are taken from my book, Expand Your Mind - Improve Your Brain about another enzyme that seems to reverse the damages of the amyloid plaque.]

It was discovered that people over ninety years of age with excellent mental capacities have higher levels of the enzyme acetylcholinesterase (AChE) in their brains. Researcher Marsel Mesulam (and a team), when at Harvard (before going to Northwestern University) identified the enzyme called acetylcholinesterase.

This discovery is very significant in the field of cognitive science, and you may soon see what is keeping neurotransmitters from working properly. Neurotransmitters have two types of effects, depolarization or hyper-polarization. The post-synaptic ions determine the effects of some transmitters. There are four transmitter substances: acetylcholine, monoamines, amino acids, and peptides.

AChE is an enzyme that works on acetylcholine (Ach) to degrade it and terminate its action. ACh is released at the synapses and exerts a post-synaptic effect upon receptors it stimulates. Acetylcholine is involved with learning and recall, as well as in controlling the stage of sleep during which dreams occur. In order to maintain high levels of acetylcholinesterase in your brain, it is imperative to prevent as many toxins as possible from entering your body.

Neurotoxicity in the brain is literally caused by toxins that have made it past the blood brain barrier (BBB). Other toxins can be manufactured in the brain because of communication problems with neurons. These neurotoxins wreak havoc with the production of the enzyme acetylcholinesterase, as explained in a paper by J Rank, K K Lehtonen, J Stand, and M Laursen published in June, 2007, by the Roskilde University of Roskile, Denmark, entitled DNA damage, acetylcholinesterase activity and lysosomal stability in native and transplanted mussels (Mytilus edulis) in areas close to coastal chemical dumping sites in Denmark.

Now for today�s article:

- - - - - - - - - - - - - - - - -

Slow Starvation of Brain Triggers Alzheimer's

By LiveScience Staff

posted: 24 December 2008

[Go to the NEWS Section of www.endowmentmed.org for all the graphics that may not be available in the Sugar Science Forum. You may also be able to download pdf documents from that website.]

A 3-D image of brain atrophy differences in mild cognitive impairment (MCI) patients and mild Alzheimer's disease patients. Alzheimer's patients show far more damage overall, especially in cortical areas of the brain. Credit: Dr. Liana G. Apostolova, David Geffen School of Medicine at UCLA

A slow starvation of the brain over time is one of the major triggers of the biochemistry that causes some forms of Alzheimer's, according to a new study that is helping to crack the mystery of the disease's origins.

An estimated 10 million baby boomers will develop Alzheimer's in their lifetime, according to the Alzheimer's Association. The disease usually begins after age 60, and risk rises with age. The direct and indirect cost of Alzheimer's and other dementias is about $148 billion a year.

Robert Vassar of Northwestern University, the study's lead author, found that when the brain doesn't get enough of the simple sugar called glucose - as might occur when cardiovascular disease restricts blood flow in arteries to the brain - a process is launched that ultimately produces the sticky clumps of protein that appear to be a cause of Alzheimer's.

Working with human and mice brains, Vassar discovered that a key brain protein is altered when the brain's supply of energy drops. The altered protein, called eIF2alpha, increases the production of an enzyme that, in turn, flips a switch to produce the sticky protein clumps.

"This finding is significant because it suggests that improving blood flow to the brain might be an effective therapeutic approach to prevent or treat Alzheimer's," Vassar said.

The best ways to improve blood flow to the brain and thereby reduce the chances of getting Alzheimer's is to reduce cholesterol intake, manage high blood pressure and exercise, especially entering mid-life.

"If people start early enough, maybe they can dodge the bullet," Vassar said. For people who already have symptoms, vasodilators, which increase blood flow, may help the delivery of oxygen and glucose to the brain, he added. The study is published in the Dec. 26 issue of the journal Neuron.

No candy bars

When it comes to prevention of Alzheimer's, eating candy bars is not the solution to improving the flow of blood glucose to the brain, Vassar told LiveScience.

A decreasing blood flow to the brain happens over time, as we age, and that slowly starves the brain of glucose. This could be a general aging phenomenon, or it could be that some individuals are particularly prone to it, Vassar said. Also, decreased blood flow is associated with atherosclerosis, or hardening of the arteries, and hypertension, or high blood pressure.

"We need to improve our cardiovascular health, not eat more sugar," Vassar said. "What is coming out in terms of the epidemiological studies is that exercise during mid-life is one of the best prevention strategies for Alzheimer's disease, so people should stay active physically, and they should watch their diets and reduce cholesterol intake, because cholesterol contributes to atherosclerosis, and that is true for the heart and the rest of the body as well as for the brain."

Vassar said it also is possible that drugs could be designed to block the elF2alpha protein that begins the formation of the protein clumps, known as amyloid plaques.

Earlier Alzheimer's findings

Ten years ago, Vassar discovered the enzyme, BACE1, that was responsible for making the sticky, fiber-like clumps of protein that form outside neurons and disrupt their ability to send messages.

But the cause of the high levels of the protein in people with the disease has been unknown. Vassar's new study now shows that energy deprivation in the brain might be the trigger starting the process that forms plaques in Alzheimer's.

Vassar said his work suggests that Alzheimer's disease may result from a less severe type of energy deprivation than occurs in a stroke. Rather than dying, the brain cells react by increasing BACE1, which may be a protective response in the short term, but harmful in the long term.

"A stroke is a blockage that prevents blood flow and produces cell death in an acute, dramatic event," Vassar said. "What we are talking about here is a slow, insidious process over many years where people have a low level of cardiovascular disease or atherosclerosis in the brain. It's so mild, they don't even notice it, but it has an effect over time because it's producing a chronic reduction in the blood flow."

Vassar said when people reach a certain age, some may get increased levels of the enzymes that cause a build-up of the plaques. "Then they start falling off the cliff," he said.

A 3-D image of brain atrophy differences in mild cognitive impairment (MCI) patients and mild Alzheimer's disease patients. Alzheimer's patients show far more damage overall, especially in cortical areas of the brain. Credit: Dr. Liana G. Apostolova, David Geffen School of Medicine at UCLA.

http://www.livescience.com/health/081224-starvation-alzheimers.html