RIGHT: The Alzheimer's brain, seen from the front, shows considerable shrinkage. The grooves, called sulci (plural of sulcus), are wider and the gyri (plural of gyrus), are smaller. The ventricles, chambers containing cerebrospinal fluid, are larger. In early stages, short-term memory begins to deteriorate when the cells in the hippocampus degenerate. As Alzheimer's spreads through the cerebral cortex (the outer layer), judgement and language decline, and emotional outbursts may occur.

Courtesy Alzheimer’s Disease Research, a program of BrightFocus Foundation

Killing the root
Gardeners know that weeds are best eradicated from the root -- chop off the top, and they usually spring right back. Similarly, the best treatment for Alzheimer's disease would halt the pathological process as early as possible, rather than treat symptoms.

For the first time, there's progress on this front. In July, 1999, Elan Corporation scientists reported that they had immunized mice against a fragment of the beta amyloid protein. Beta amyloid is the insoluble gook in the plaques which clog the brain in Alzheimer's. Despite some debate, many scientists think that amyloid plaques kill neurons.

In the Elan experiment, immunization prevented Alzheimer's from getting started in mice that were genetically programmed to get it. Intriguingly, the vaccination also seemed to reverse the brain pathology in older mice whose disease had already begun.

The researchers concluded that the vaccine caused mice to mount an immune response against beta amyloid. Elan has started recruiting 48 Alzheimer's patients for a study of the safety with the vaccine.

Engaging enzymes
Over the past decade, scientists have been looking for the enzymes that scissor beta fragment from a larger hunk of protein. If beta amyloid indeed kills neurons, inhibiting these enzymes could play a major role in fighting Alzheimer's.

After numerous efforts to isolate the enzyme, scientists at Amgen, a California biotech firm, have apparently succeeded in finding the gene that makes the enzyme (see "Enzymes Point Way... " in the bibliography).

Rather than searching directly for a protein that would boost beta amyloid production, the researchers added several genes to a cell culture while monitoring beta amyloid production. After eliminating genes that simply boosted the raw material for beta amyloid, they found one that seems to make the long-sought enzyme.

With at least one enzyme identified -- more may be involved -- the next step is to search for chemicals that will inhibit it, reducing the level of destructive beta amyloid. That work is ongoing in university and industry labs.

Growing new neurons
For decades, scientists have maintained that new neurons do not form in the brain of adult mammals. As The Why Files covered, that dogma is dead. Then last fall, in a finding that could lead to new methods for treating brain diseases and injuries, scientists showed that new neurons are continually added to the cerebral cortex of adult monkeys. The cerebral cortex is the largest and most advanced part of the brain. As the site of reasoning and memory, it is responsible for high-level decision making and for learning about the world.

Last October, Elizabeth Gould and Charles Gross reported that new neurons occurs in several parts of the cerebral cortex that are crucial for cognitive and perceptual functions (see "Neurogenesis in the Neocortex... " in the bibliography).

The results strongly imply that the same process occurs in humans, because monkeys and humans have fundamentally similar brain structures. If the all-important cerebral cortex can accept new neurons, then the idea of using stem cells to replace neurons becomes that much more plausible -- but still as much as a decade away from the clinic.

Can't wait decades? How 'bout some simple solutions for preventing this miserable disease?