Prion is pronounced prē'ŏn

Most people are under the impression that we do not know what causes the debilitating disease called Alzheimer's. We used to call it Senility. Doctors called it Dementia, and at one time considered it a normal part of aging. Some 50% of the population will display symptoms of this tragic disease after age eighty.

The disease was first described in 1906 by Dr. Alois Alzheimer, after whom the disease is named, after he autopsied the brain of a 51 year-old patient who showed severe symptoms of dementia and brain dysfunction and who died completely unresponsive to treatment. He noticed the characteristic 'plaques' and 'tangles' as he called them, evidence of the devastating destruction of what should have been a system of healthy neural networks in the brain of a woman too young to die.

Fast forward to 1976: Daniel Carlton Gajdusek wins the Nobel prize for his research on Kuru, a disease very similar to Alzheimer's, found primarily among the South Fore people of New Guinea, a native tribe which practised ritual cannibalism. It was found that females of the tribe were more likely to contract the disease, and he concluded that this was the result of eating the brains and other soft organs of their deceased. It was customary to allow the women and children first access to their dead relatives. The men would later indulge primarily in the fleshy portions. About eight times more women than men contracted the disease. Studies on the brains of the deceased victims of Kuru showed similar plaques and tangles. Obviously there was a connection between cannibalism and Kuru.

Fast forward again to 1997: Stanley B. Prusiner wins the Nobel prize in Physiology or Medicine for his discovery of the prion. Prions are the misfolded proteins that lie at the root cause of Alzheimer's disease, Creutzfeld-Jakob's disease, Kuru, and BSE, or Bovine Spongiform Encephalopathy as well as Scrapies, a similar disease affecting only sheep. He coined the term prion, which is a shortened form for 'proteinaceous infectious particle that lacks nucleic acid'.

Beef cattle farmers had for a long time supplemented the feed of their cattle with the reconstituted protein derived from the remains of sick and downed livestock, which were considered unfit for human consumption. Chicken farmers supplemented their chicken feed with the fecal remains of their own chickens, which was also high in protein. This practise made for a more robust, meatier animal, higher in monetary value than one whose diet was not supplemented in this way. By 1997 this practise was outlawed across the western world, and the link to BSE, or Mad Cow disease, and the resulting human form of the variant Creutzfeld-Jakob disease was officially recognized.

As stated, Alzheimer's disease is a prion disease. The prion is a mutant form of the peptides that are found throughout the body. In fact, there is no essential difference between the neural peptides found in the brain and the intestinal peptides. They are merely linear amino acid chains produced by the template action of genes found on chromosomes 11, 15, and 21. When a cell requires the raw materials for the normal synthesis of proteins, which are complex molecules constructed of amino acids, it pulls in a peptide through the hydrophobic cell wall, so they actually provide the vital service of supplying the raw materials for protein synthesis. They can themselves be considered simple proteins because all it takes to qualify for that definition is that they be a molecule constructed of amino acids.

The process by which these peptides become misfolded was described by the late great Vernon M. Ingram, professor of microbiology, in this article in which he traces the progression of Alzheimer's disease at the molecular level and which can be found in the July-August, 2003 issue of the journal American Scientist. I will briefly describe that process.

The prion which is known to cause Alzheimer's begins as a normal peptide. Enzyme activity within the hydrophobic layer of the neuron cell membrane cleaves the peptide at a location which results in the inability of the internal cellular machinery to properly identify the peptide as a source of amino acids and the peptide is discarded and evicted from the cell. This enzyme action is puzzling to microbiologists because enzymes can only do their work in the presence of water, and the term hydrophobic means 'fear of water'; ie. there is no water molecule present where cleavage was found to take place.

The evicted mutant peptide has 'sticky' properties and forms aggregates with others of its kind. These 'plaques' gather around the calcium ion channels of the cell wall and prop them open which results in a flood of calcium ions into the cell, which spells disaster. These calcium ions act on the tau protein in the neuron and their action compromises the integrity of the scaffolding which serves as the three dimensional skeletal structure of the cell. The cell collapses, and either performs apoptosis, which is cell suicide, or it just ruptures. Either way, a link in what might be an important chain of neurons in the network is now broken. The neurons have a backup mechanism in the form the neurotransmitter acetylcholine, which takes over the task of carrying information to the next cell in the chain, after which the acetylcholine molecule is broken down by the enzyme acetylcholine-esterase, a necessary measure to prevent the overabundance of neurotransmitters from upsetting the balance of messages sent and received by the neurons. This is why acetylcholine-esterase inhibitors form an important line of defense in the treatment of the progression of the disease.

As to how the original action on the peptide in the hydrophobic layer of the cell occurs in the absence of a water molecule might be explained by the following discussion, but keep in mind that this is completely my own theory and not officially acknowledged. For background information one would do well to view and study this slide show about how the recreational drug Ecstasy acts on the brain.

In short, when a receptor site on a host cell is overstimulated, it becomes tired and evicts the molecular blocker, which in the slide show example is serotonin, and then the receptor withdraws into the cell to regenerate. I believe that something similar happens to the receptor sites on the red blood cell. The red blood cell is not really a cell at all because it lacks a nucleus. It is a large molecule containing an iron ion at its center and at least four receptor sites on its surface to which bind oxygen or carbon dioxide molecules and which is responsible for completing the respiration process by transporting O2 and CO2 to and from the cells and lungs. These receptor sites are active 24 hours a day every day of one's life and I think that it is possible that these sites also sometimes get tired, and/or the iron ion loses its efficacy over time and an errant oxygen molecule will occasionally drop off. Oxygen is electrostatic and will form ionic bonds with certain places on certain molecules. I believe that the abnormal cleavage sites on the normal peptides are areas to which those oxygen molecules have bound themselves, and when the peptide passes through the hydrophobic layer the oxygen will combine with the hydrogen molecules there to form a water molecule, thereby facilitating the enzyme's action on the peptide.

So, in a sense the development of Alzheimer's disease in an individual of advanced age can indeed be considered part of the normal aging process. I believe that a radical treatment involving complete replacement of hemoglobin with rejuvenated blood product might be an effective treatment for prion related diseases but, admittedly, I speculate.