1. Archive

Major piece of Alzheimer's puzzle found

Alzheimer's disease is slowly beginning to surrender its terrible secrets.

There is still no cure and no effective treatment, but armies of gene researchers around the world are closing in on some of the causes of the disease.

A major breakthrough, "an important piece of the puzzle," is announced today in the journal Nature. Researchers from the University of Toronto say they have discovered the gene responsible for the most severe form of the disease, one that strikes people as young as 30.

While this "early-onset" form is rare _ afflicting 5 to 10 percent of people who develop the disease _ scientists believe it will tell them much about the more common forms of Alzheimer's that strike larger numbers of people later in life.

All forms of Alzheimer's cause dementia and memory loss. About 4-million Americans suffer from the disease.

The discovery of mutations of a gene on Chromosome 14 was a personal triumph for Dr. Peter St. George-Hyslop and collaborators from the United States, Canada, the United Kingdom, France and Italy.

For hundreds of other researchers engaged in a competitive hunt for the same gene, the news came first as a disappointment, then a challenge to use the new knowledge to make new discoveries.

"It's a major breakthrough," said John Hardy of the University of South Florida. "I'm glad it happened. I'm sorry it didn't happen here."

"I've been working on this for the last two years, and yes, I'm disappointed," said Mike Hutton, who, with Hardy, leads the USF effort. "But this is only the start of the work. There's a vast amount to do. This clearly opens up a new avenue of Alzheimer's research."

Hardy came to USF from England several years ago. He and Michael Mullan, another USF gene researcher, are credited with finding three mutations in a gene on Chromosome 21 linked to Alzheimer's.

For all its notoriety, very little is known about how Alzheimer's disease develops.

Genetic makeup, environmental factors and sometimes interaction between the two are thought to be the causes of most forms of the disease.

However, the cause of early-onset Alzheimer's is thought to be purely genetic. This is important, because it would mean that the newly discovered gene "is very likely a fundamental and important step in the biochemical process that causes all types of the disease," St. George-Hyslop said in a statement.

Hearing rumors of the news a few days ago, Hardy, Hutton and other members of the USF team began working around the clock in their own labs to confirm the University of Toronto findings.

The St. George-Hyslop team reported finding five mutations of the gene, Hardy said, each linked to development of early-onset Alzheimer's. "But we think there may be many more _ perhaps from 10 to 50" mutations of the gene, Hardy said.

Finding the mutations, however, doesn't explain the role they play in the development of the disease. That's still a mystery.

It is not yet known, for example, whether the mutated gene causes the disease, or whether a healthy gene inhibits the disease in some way the mutated gene cannot.

"Understanding these relationships will help us understand all types of Alzheimer's disease," said Hardy. "We expect this gene to tell us a great deal."

"Up until now," said St. George-Hyslop, "all we've been doing is guessing."

"This is an exciting time," said Hardy.

_ Information from Times wires used in this report.