Shutting Down Alzheimer's
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New research reveals strategies for blocking the molecular processes that lead to this memory-destroying disease. By Michael S. Wolfe

The human brain is a remarkably complex organic computer, taking in a wide variety of sensory experiences, processing and storing this information, and recalling and integrating selected bits at the right moments. The destruction caused by Alzheimer's disease has been likened to the erasure of a hard drive, beginning with the most recent files and working backward. An initial sign of the disease is often the failure to recall events of the past few days--a phone conversation with a friend, a repairman's visit to the house--while recollections from long ago remain intact. As the illness progresses, however, the old as well as the new memories gradually disappear until even loved ones are no longer recognized. The fear of Alzheimer's stems not so much from anticipated physical pain and suffering but rather from the inexorable loss of a lifetime of memories that make up a person's very identity.
Unfortunately, the computer analogy breaks down: one cannot simply reboot the human brain and reload the files and programs. The problem is that Alzheimer's does not only erase information; it destroys the very hardware of the brain, which is composed of more than 100 billion nerve cells (neurons), with 100 trillion connections among them. Most current medications for Alzheimer's take advantage of the fact that many of the neurons lost to the disease release a type of chemical communicator (or neurotransmitter) called acetylcholine. Because these medicines block an enzyme responsible for the normal decomposition of acetylcholine, they increase the levels of this otherwise depleted neurotransmitter. The result is stimulation of neurons and clearer thinking, but these drugs typically become ineffective within six months to a year because they cannot stop the relentless devastation of neurons. Another medication, called memantine, appears to slow the cognitive decline in patients with moderate to severe Alzheimer's by blocking excessive activity of a different neurotransmitter (glutamate), but investigators have not yet determined whether the drug's effects last more than a year.

More than a decade ago few people were optimistic about the prospects for defeating Alzheimer's. Scientists knew so little about the biology of the disease, and its origins and course were thought to be hopelessly complex. Recently, however, researchers have made tremendous progress toward understanding the molecular events that appear to trigger the illness, and they are now exploring a variety of strategies for slowing or halting these destructive processes. Perhaps one of these treatments, or a combination of them, could impede the degeneration of neurons enough to stop Alzheimer's disease in its tracks. Several candidate therapies are undergoing clinical trials and have yielded some promising preliminary results. More and more researchers are feeling hope--a word not usually associated with Alzheimer's.

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