Could Alzheimer’s Disease be Genetically Programmed?

We often say when describing the actions of a patient suffering from Alzheimer’s Disease (AD) that they are behaving like a child.  They throw the same kind of tantrums, they often don’t understand situations, they deny responsibility for things that they have done, and so on. Up to now no-one has come up with a convincing theory of what the causative mechanism of AD really is.  Yes, there have been findings of plaques or tangles of various proteins in the brains of AD sufferers, but no-one knows if they are causative or secondary by-products of AD.

One fact that is known is that the brains of most AD patients shrink quite dramatically. Now it occurred to me that the brains of humans grow from childhood through teen years and develop significantly into adulthood.  This is clearly a genetically controlled process, during which brain cells develop and very many synapses are made. These then constitute the connections that make the adult human brain so powerful, both in cognitive ability and memory.  These are precisely the two main functions that are lost with the onset and development of AD.

It occurred to me that the process of AD could be a reversal, not necessarily exact, of the genetically controlled process of brain development and growth.  Suppose there is a trigger that initiates a process that causes brain development to reverse.  This might explain the puzzling findings that the brains of some sufferers from AD do not shrink significantly, while other people without AD do have shrunken brains.  It may depend not on the actual size of the brain, but what brain cells die and what synapses are lost. If there is such a process, it must be genetically controlled, a kind of reversal of brain evolution.

This might be considered parallel to the process of cell death known as apoptosis.  It was discovered in the 1950’s that certain cells spontaneously die by a genetically controlled process termed programmed cell death or apoptosis that starts with specific changes to the cell’s biochemistry (with the formation of specific proteases called caspases and then production of specific endo-nucleases that degrade the cell’s DNA in a characteristic manner into units of a certain uniform size).   What is somewhat mysterious about this process is that in a given organ or cellular structure, as cell’s divide other cells enter apoptosis, but it is impossible to predict which ones in a large cell cluster will be the ones to die in this manner.  It is similar to a nuclear reaction in which a certain number of atoms will spontaneously split according to a precise mathematical equation, but it is impossible to predict which ones will do so.

There is a known rare early onset form of AD that is familial and therefore inherited and results from mutations in specific chromosomes. But, perhaps generally AD is a result of a genetically controlled process of brain regression that nominally reverses the process of brain development.  This is only a conjecture, but perhaps one that is worth pursuing.

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