The Biology of Death (#2) The Biology of Death (#2)

Wrapping up reading "The Biology of Death" that I mentioned in an earlier post. Ran into an interesting factoid.

Somewhere around four years ago, my girlfriend's father had surgery for Alzheimer's. The surgeon claimed that this experimental procedure had a chance of stabilizing his condition for four or so years, as it apparently has. Almost like clockwork, it seems that her father is starting to progress again.

At the time, I asked around about this, including of some physician friends of mine who treat this affliction. Also, I looked on the Internet for any indication of this procedure, or, indeed, why it might work. I kept coming up blank.

But today, I think I have the answer. One of the things that investigators have been looking at in trying to figure out why we die is the death of cells. Cells can either be killed ("necrosis"), or they can commit suicide ("apoptosis"). Apoptosis is necessary for creation of multicellular life. For example, when fingers are being formed in utero, essentially stumps are formed, then the fingers are etched into the stumps via programmed apoptosis. Similarly, the routing of the brain uses extensive apoptosis.

Extensive work is being done on apoptosis right now - on how it is turned on, and how it is prevented. Different genes have been identified for both, as have different enzymes.

Interestingly, cancers had been assumed to be the result of uncontrolled growth. But apparently a number of cancers appear instead to be the result of a supression of apoptosis. Apparently, one of the body's mechanisms for controlling tumors is for them to either voluntarily commit suicide, upon detection of genetic damage, or do it upon order of the immune system or their neighbors. One of the most widely studied tumor supression genes is p53. Apparently, the deregulation of p53 is one of the primary causes of cancer in humans: fully half of all cancers diagnosed, taken as a whole, are somehow related to mutations of this gene. Mutations of this gene have been found in more than fifty types of cancer, including those affecting breast, brain, lung, colon, skin, and prostate.

Back to Alzheimer's. That condition is the result of neurons dying. It was long assumed that they were killed somehow, partially due to lack of evidence of apoptosis. But the evidence of such would, by necessity, be extremely transistory, being cleaned up within hours of cell death. Closer examination has shown that apoptosis is, indeed, involved.

Overall, it is unclear why those neurons commit suicide. But one of the major features of the brains of Alzheimer's patients is the presence of numerous spherical aggregates measuring approximately one hundred microns in diameter, called "senile plaques". In 1985, one of the major components of these senile plaques was discovered: a small, hydrophobic peptide composed of 39 to 42 amino acids and called "amyloid peptide". Interestingly, although the function of amyloid peptides are still largely unknown, it has been shown that they can trigger apoptosis of the neurons in the area where they accumulate. Though somewhat convoluted to a layman such as me, it appears that this phenomenuon can self-intensify due to the side effects of apoptosis.

In other words, what appears to (maybe) be happening in Alzeimer's patients is that neuron apoptosis indirectly results in amyloid peptides which ultimately results in more neuron apoptosis. But it is the senile plaques where the amyloid peptides are concentrated. Thus, by removing them, the amount of amyloid peptides is reduced, significantly reducing the neuron apoptosis, and, thus, stabilizing Azheimer's patients until the senile plaques build up again.

And, that is indeed what the brain surgeon appears to have done to my girlfriend's father - the surgeon's removal of senile plaques resulted in a temporary stabilization my girlfriend's father's Alzheimer's (how do you like that - three possessives in a row). Her explation wasn't quite accurate, as she said that the plaques "poisoned" the neurons, which would have implied necrosis, and not apoptosis, which is actually the case. But close enough.