New Gene Linked to Alzheimer's

Scientists have found a gene that, when damaged, may increase the risk of developing late-onset Alzheimer's disease, the most common form of the disorder which strikes people over 70. The scientists estimate that 30 percent of the population carries the mutant gene, but caution that it cannot be used to predict or diagnose Alzheimer's.

"It could be a powerful new target for the development of drugs to prevent or treat this disease," said Rudolph Tanzi, director of the Massachusetts General Hospital Genetic and Aging Unit, whose report on the gene appears in the August issue of the journal Nature Genetics.

Such a drug would interfere with a series of interactions in the brain that lead to the development of toxic proteins associated with Alzheimer's.

When functioning normally, the gene produces a protein called alpha-2-macroglobulin, which controls the activity of other proteins that sweep up those toxic proteins, including amyloid-beta, preventing them from attacking brain cells.

The mutant version of the gene does not produce the sweeping protein, leaving the toxic proteins free to cause damage.

The researchers from Massachusetts General Hospital, the School of Public Health, and other institutions used a new statistical method to track down the gene in a group of families predisposed to Alzheimer's. Now the scientists hope to see their results duplicated in other groups of people as well.

Deborah Blacker, assistant professor of psychiatry at Massachusetts General Hospital, and the paper's lead author said, "In addition to what it may tell us about the disease process, this finding -- if replicated -- will help us sort out the role of additional genetic and environmental factors in future studies."

Alzheimer's Protein Strikes the Elderly

Fibrous proteins found in the brains of Alzheimer's victims have been suspected as the cause rather than the result of the disease. Harvard researchers have added weight to this theory by examining the damage created by the protein amyloid-beta in animals.

"A central issue is whether or not amyloid-beta is a cause of neuronal degeneration in Alzheimer's disease," said Bruce Yankner, associate professor of neurology at Harvard Medical School and Children's Hospital, who authored the study in the July issue of the journal Nature Medicine along with Changiz Geula, assistant professor of medicine at Beth Israel Deaconess, and their colleagues.

In nonhuman primates they found that the protein amyloid-beta at a level similar to that in Alzheimer's destroys healthy nerve cells, creating a concentric pattern of destruction in the brain. The nerve cells surrounding the protein died in a manner which is similar to the damage caused by Alzheimer's.

The researchers also found that the protein was only toxic in aged animals and had no effect in young animals, which were shielded from toxic effects by unknown factors. In addition, the closer the animals were related to humans, the more damage the protein caused.

"The study provides future directions for investigation," said Yankner. "If we can learn why the aging brain, but not the young brain, is susceptible to the toxic effects of amyloid-beta, we may be able to target the susceptibility factor with drugs."