The exact physiological processes that take place in Alzheimer's disease are still in dispute, but in general terms we can say that there are random disruptions of the connections in various networks in the brain. The tangles of neural axons and dendrites that are found upon post-mortem dissection of the brains of Alzheimer's patients are like tangles of wires in an electrical appliance. Just as an appliance cannot function properly if its wires are not laid out properly, so the brain cannot function if its neurons are not connected properly.

	Thinking Point
	Personality changes can result from accident or illness, as in the example of Phineas Gage, but do such changes make people different at a more fundamental level?

But this analogy is only partial. The networks in the brain do not just send information from one place to another. All the information there is in the brain--not just knowledge about the world, but all our capacities to do the things that require a brain, from walking upright to going shopping to cooking meals to discussing philosophy over dinner--is located within the networks themselves. An accumulation of random disruptions of the connections in any network will lead to increasingly erratic behavior of various sorts, ending in the inability to do anything at all.

The tangles in the networks that constitute Alzheimer's are quite different from the ordinary death of neurons. We are constantly losing neurons, but the loss of a few of them does not substantially change the functioning of any given network. In normal aging many neurons die, and this may be one reason why it becomes harder to learn new things as we get older. But as long as the remaining neurons retain their proper connections, we can still do all the things we could do before, even if it may take a little longer.

The way Alzheimer's differs from normal aging is that the neurons don't just die and disappear--instead, the axons and dendrites that connect them become tangled up. In normal aging, some of the connections that have activated the pattern yielding the name 'Judith' when I see my friend may be lost, and so it may take a little longer than usual for me to recall her name. The remaining connections will still be intact, however, so I will not mistake her for someone else. But if John, say, has Alzheimer's, then the axon branches coming from the human-face network that are supposed to activate some dendrites in the human-name network to allow John to say 'Jerry' when he sees his friend may become tangled up with other axon branches in the face network. This may lead to a situation in which several different patterns in the name network are slightly activated at the same time, with no one of them being activated sufficiently to allow the neurons to form one stable pattern for one particular name. John will thus be unable to recall Jerry's name. As the tangling of the dendrites and the axon branches spreads to other areas of John's brain, he may no longer recognize Jerry as his friend at all. Later, even though he may still be able to talk, he may not recognize his own children when they come to visit him. They may seem familiar, but he will not remember how they are related to him. Later still he will not be able to perform even the simplest functions.

The loss of function in patients with Alzheimer's does not always occur in the same order, as the random tangles may begin in different areas of the brain and spread in different ways, but in the end the entire brain is affected.

Until very recently the accepted wisdom in biology was that nerves in the central nervous system, which includes the brain and the spinal cord, can never regenerate. That is, once they are damaged, the damage is permanent--the damaged cells cannot repair themselves, and the undamaged cells cannot divide to provide new cells.

Our skin, for example, repairs itself after injury in that the undamaged cells divide rapidly to provide new healthy cells that take the place of the damaged ones. In cases where so much skin is damaged that this process cannot provide enough new cells, skin can be taken from another part of the body to cover the injured area, and the cells in this graft will divide in their new home and connect up with the ones already there. This is a relatively easy process because skin cells are connected to their neighbors very simply--all they have to do is touch each other snugly, as their main function is to protect the body parts underneath them.

Nerve cells, in contrast, generally stop dividing around the time of birth. Learning, as we have seen, takes place through the selective strengthening of connections between neurons, and does not require the growth of new cells. And until very recently it was believed that the neurons cannot be stimulated to divide again, even in the case of injury.

In the past few years, however, there have been hints that a way can be found to make the neurons in the spinal cord start dividing again after an injury. This technique is still in the laboratory stage, and has not yet been refined enough to start using it in injured people, but let us assume that it will someday be used in patients. Such an advance might be possible because the nerve cells in the spinal cord are connected to one another in fairly fixed ways. These neurons are merely messengers that allow the brain to tell the muscles what to do. They normally form connections with one another before birth, and these connections are not changed by the learning process. When we learn to walk, say, changes occur in neural connections in the motor networks of the brain and in the cerebellum, the area at the base of the brain responsible for fine-tuning our movements. The connections between the neurons in the spinal cord, however, remain fixed. Thus if there is some way to get these neurons to regenerate after they have been damaged, it is plausible that they might be able to reconnect to one another in the way they did when they were first developing, and this may be enough to allow the patient to walk once again.

The situation in the brain, though, is far more complex. The connections between the neurons are changed by everything we learn during our lives, and these changed connections actually constitute our knowledge. Thus if they become tangled up, there is no way to untangle them. Even if the remaining healthy neurons could be made to divide by some spectacular medical breakthrough, the odds would be astronomical against any new connections they made being the right ones. Since these connections were all established by a slow learning process in the first place, any reconnection would require a similar slow learning process.

Indeed, the evidence of occasional recovery from serious brain damage offers strong support for this claim. Some people who have been in a coma for a long time, generally after suffering brain damage due to the brain being starved of oxygen for too many minutes, do eventually regain near-normal functioning. But this requires a lengthy learning period, in which the patient must learn to walk, talk, feed and dress himself, all over again. In such cases many of the connections have apparently remained intact while others were damaged, so that the patient's expert knowledge in a particular field may be preserved and become available once again when the patient becomes able to access it.

Thus if some way were found of making the neurons in the brain divide, the most that could be hoped for in the case of Alzheimer's patients would be that they could start the process of learning all over again. But since in the case of Alzheimer's, unlike the case of oxygen starvation, the patient's knowledge about the world is often one of the first casualties of the disease, it would probably take as many years to relearn all this knowledge as it took to learn it in the first place. And since even the brains of normally aging individuals have trouble making the changes that are required for learning a great deal of new material, the prospect of restoring Alzheimer's patients to their former situation seems extremely remote.