Genetic Clues

Among the afflictions of old age, Alzheimer's is a particular affront. The degenerative mental condition, which affects some 2 million people in the U.S., robs its victims of their dignity and renders them helpless. They become confused, lose track of time and are eventually unable to recognize spouses and other loved ones. Physiologically, Alzheimer's manifests itself in the form of abnormal protein deposits in the brain. But the reason these insidious tangles and plaques build up remains unknown.

Last week an international team led by scientists at Massachusetts General Hospital and the National Institutes of Health announced in the journal Science that they had discovered an important clue to the mystery. Aware that at least 10% -- and perhaps as many as 70% -- of Alzheimer's cases are inherited, the researchers began analyzing the DNA from four large families that had one thing in common: a history of the disease stretching back over many generations. After three years of work, they isolated two genetic markers, or molecular signposts, on chromosome 21 that are located close to the still unknown gene responsible for the inherited form of the disease. "The identification of these markers overcomes a major hurdle," says M.G.H. Neurogeneticist James Gusella, who directed the research. "This is the first step toward the identification of the primary cause of the disease." (Gusella has another claim to fame: he headed the group that in 1983 found the long-sought marker for Huntington's disease.)

The scientists had focused on chromosome 21 because of its connection with Down's syndrome, a genetic defect that is the nation's leading cause of mental retardation. Most Down's victims have three copies of this chromosome rather than the normal two, and by age 40 their symptoms often include the now familiar protein deposits in the brain.

Within the past two weeks four separate groups of researchers disclosed that they had isolated a gene, also on chromosome 21, that is responsible for the protein in the deposits. The proximity of the markers to the gene suggests either that the protein, which is called amyloid, is the cause of Alzheimer's * or that the amyloid gene lies in the vicinity of the gene responsible for the inherited form of the disease.

If further research proves that the amyloid protein is the cause of Alzheimer's rather than just a symptom of the disorder, researchers could begin the search for a drug to curb its production. The markers found by Gusella's team could lead to even more immediate results: isolation of the gene that causes familial Alzheimer's. And this would enable doctors to identify some victims of the disease before their symptoms appear.