FOR YOUR INFORMATION

FROM

THE SAN FRANCISCO MEDICAL RESEARCH FOUNDATION

The enigma of Alzheimer's disease has intrigued neuroscientists and neurologists since its first description by the neuropathologist Alois Alzheimer in 1907. One of the earliest observed pathological features was the appearance of microscopic changes in the brains of affected individuals. These included dark staining material called "senile plaques" and twisted strands of filaments called neurofibrillary tangles.

Unfortunately, most research to date has centered around these microscopic accumulations of debris within certain brain cells as the possible cause of Alzheimer's disease.

These so-called "inclusions" have been examined by electron microscopy and subjected to sophisticated biochemical analysis. The conventional wisdom has concluded that the affected brain cells in Alzheimer's dementia are destroyed by the slow accumulation of these inclusions. It makes for a nice theory, but unfortunately there are major problems with this scenario. If plaques are the cause of dementia of the Alzheimer's type, then any brain found with large numbers of them should be accompanied by dementia. In fact, perfectly normal individuals may have large numbers of these inclusions.

Unfortunately, research tents to follow the grant money. Those scientists promoting the theory that Alzheimer's disease is caused by plaques are also the ones responsible for distribution of grant monies. While not always doing so directly, they make recommendations to government and private granting institutions as to who should get research money. This, unfortunately, excludes those who have ideas outside the mainstream.

Of equal concern is the fact that the same individuals who control research grant dispersal also control the editorial staffs of most scientific publications. Scientists having a new approach to this problem are frequently excluded from such journals. The lay media turns to the "leading authorities" in the field for interviews and features on such stories. These leading authorities are the same individuals who are promoting their pet theories connecting Alzheimer's disease to plaque formation in the brain.

THE LINK BETWEEN ENERGY DEPRIVATION AND DEMENTIA

There is growing evidence that brain cell changes of Alzheimer's dementia begin long before obvious symptoms develop, perhaps as early as the fetal stage. In examining over 40 studies on brain cell energy production in Alzheimer's disease, one common denominator that emerges is the failure of important energy-producing enzymes in the brain cells. Involved are cytochrome oxidase (complex IV), pyruvate dehydrogenase complex, transketolase and ketoglutarate dehydrogenase complex. The last three are thiamine dependent enzymes.

What this means is that these enzyme deficient brain cells are unable to produce enough cellular energy to support themselves. I discussed this process in detail in Excitotoxins: The Taste That Kills. But what is especially important is the observation that cellular protective mechanisms require tremendous amounts of energy. Numerous studies have shown that when this energy system fails, the cells begin to rapidly die, and over many years reaches a certain irreversible stage when dementia develops.

Further evidence comes from the observation that when otherwise normal brain cells are made energy deficient, by whatever means, they not only die but they produce plaques and neurofibrillary tangles, just like those seen in human Alzheimer's dementia. Another interesting observation is that the microscopic "plaques" seen in Alzheimer's brains are composed of broken bits of mitochondria (the energy producing system of the cell) and lysosomes. Lysosomes are in essence "suicide packets." When a cell is seriously damaged, destructive enzymes from these packets are released so as to literally dissolve the damaged cell. These findings indicate that plaques are not the cause of the disease but rather the final result of the disease.

HYPOGLYCEMIA AND DEMENTIA

At least two well conducted studies have shown that personas developing Alzheimer's dementia have lower fasting blood glucose levels and higher insulin levels. This is especially made worse following a glucose challenge (reactive hypoglycemia). In such individuals we often see chronic (decades), recurring spells of hypoglycemia. This would act to deprive certain brain cells of their energy supply. Remember the brain relies primarily on glucose for its energy supply. Interestingly, the one area of the brain most affected by Alzheimer's disease, the temporal lobes, also has the narrowest margin of safety between glucose supply to the brain and its needs. This would make the temporal lobes much more vulnerable to injury by hypoglycemia.

But not all hypoglycemia is obvious to the person affected. There is a condition which I call "brain hypoglycemia" in which the blood glucose may be perfectly normal while the brain itself is severely hypoglycemic. Under such conditions the person would not have the usual symptoms: trembling, intense hunger and nervousness. Instead they may experience difficulty thinking clearly, remembering details or names, and disorientation. In fact, many of the symptoms of "brain hypoglycemia" closely resemble Alzheimer's dementia.

Normally, glucose enters the brain by way of a carrier mechanism. The carrier meets the glucose from the blood at the blood-brain barrier, puts it on its back and carries it into the brain. Without the carrier the brain would starve despite there being adequate glucose in the blood. We know that as we age this carrier system becomes less efficient. In fact, there are many conditions in which the glucose carrier is impaired including Alzheimer's disease.

So we see that there are several sites at which the brain can become energy deficient: (1) insufficient glucose in the blood (hypoglycemia), (2) inability of glucose to enter the brain from the blood (brain hypoglycemia), and (3) inability of the brain cells to metabolize glucose (enzyme deficiencies).

A FINAL COMMON PATHWAY?

The ultimate question is how does a lack of glucose kill brain cells? It may not be as simple as first thought. The cells don't simply starve to death. The cell's protection system requires a large amount of energy. It appears that when the cell is unable to generate a sufficient amount, it is unable to protect itself from certain toxins. One group of toxins getting a lot of attention are called excitotoxins, including glutamate and aspartate.

When brain cells are exposed to excitotoxins in large concentrations, the cells will shrivel up and die. Under normal conditions brain cells can protect themselves from excitotoxins by certain cellular mechanisms. But we know that when brain cells are energy deficient they lose this protective ability, and under such circumstances even normal or low concentrations of excitotoxins can destroy brain cells.

Excitatory amino acids such as glutamate and aspartate normally exist in the brain in low concentrations. When the brain becomes hypoglycemic these low levels become toxic. This may be the final common pathway in a host of neurodegenerative diseases such as ALS, Parkinson's disease and Huntington's disease. These excitotoxins are also found in our food as flavor enhancing additives, such as MSG and aspartame, which can increase brain levels of these toxic compounds.

RESTORING THE BRAIN'S ENERGY

The cure for Alzheimer's disease may lie in restoring the brain's ability to generate energy. Recent studies using PET scans (which demonstrate the actual metabolism of the living brain) of affected brain areas in Alzheimer's or Huntington's patients show a decrease in energy production and glucose utilization long before the disease becomes clinically evident.

The problem with energy production appears to center itself in the mitochondria, the energy factory in the cell. A growing list of mitochrondial diseases have been discovered. Recently, doctors have been able to reverse some of these disorders by utilizing supplements known to play a part in this energy process.

One of the most effective combinations has been CoQ10, acety-L-carnitine, riboflavin, thiamine, pyrodoxine, niacinimide and ginkgo biloba. While this combination has not been adequately studied in Alzheimer's patients it holds much promise. The key would be to start the regimen very early in the course of the disease before excitotoxic damage has become irreversible.

Another compound that has shown interesting results is phosphotidylserine, one of the brain's phopholipids. It also plays a vital role in membrane functions. As we age, our cellular membranes begin to change, to become stiffer. Proper functioning of the membrane requires that it be more fluid. Phosphotidylserine appears to do just that. Interestingly, it also acts as a glutamate blocker, thereby preventing excitotoxic damage to the cell.

Those having hypoglycemia or a strong family history of one of the neurodegenerative diseases should avoid excitotoxins in their food and probably should take these supplements at an early age, beginning in their twenties or thirties. This would boost their brain's energy supply thereby protecting vulnerable brain cells from injury. I would also recommend dietary modifications.

Russell L. Blaylock, M.D., is in private neurosurgical practice in Jackson, MS, and Associate Professor of Neurosurgery at the Medical University of Mississippi. He has published numerous scientific papers, chapters in medical texts and a patient care booklet on multiple sclerosis.

(Reprint, Healthy and Natural Journal, Volume 3, Issue 2)

Copyright © 1996. The Light Party.