Scientists Progress In Alzheimer's Study

A study researched in part by an Harvard Medical School professor has shown a link between the double appearance of a certain gene and a form of Alzheimer's disease, Medical School faculty members said yesterday.

Assistant Professor of Neurology, one of the principal researches, said the study, which will be published in Science magazine today, will detail the nature of an important gene correlation related to the disease.

He said the study showed a strong correlation between the appearance of two APOE-4 alleles, which were recently shown to have a correlation with late-onset Alzheimer's disease, and the age and possibility of Alzheimer's onset in those with a family history of the disease.

The research was conducted at the Massachusetts General Hospital and at the Bryan Alzheimer's Disease Research Center at Duke University.

APOE, which is located on chromosome 19, can appear in the form of allele APOE-2, APOE-3 or APOE-4. The study's subjects, who were taken from 42 families with a history of late-onset Alzheimer's had one APOE-4 allele from each parent. The study found them eight times as likely to develop Alzheimer's.

Haines said that while a correlation between APOE-4 and an increased risk of Alzheimer's had been shown by results published earlier this spring, the high correlation between the double appearance of the gene and the occurrence of Alzheimer's was a new discovery.

"The research was taken a step further--it's been shown that it depends on how many copies of APOE-4 you have," he said.

Haines said, however, that results on research on a broader spectrum of the population have yet to be obtained. "It's in progress--we're doing it, a lot of other groups are now doing it," he said. "We'll look at the families we have that have early-onset Alzheimer's as well as the general population."

He said the research centering around APOE-4 represents "a new turn of events" in Alzheimer's research.

"The APOE gene itself was studied for a long time because it's related to an increased risk for cardiovascular disease... but it was not thought to be involved in Alzheimer's," Haines said. "It's involved in the metabolism of lipids and cholesterol--that's the known role. We suspect it may have other functions not known at this time."

But Rudolph E. Tanzi, an assistant professor of neurology and director of the lab of genetics and aging at MGH, cautioned against classifying APOE-4 as a cause of Alzheimer's based on the current research.

While he said that Haines' statement that two copies of the gene greatly increases the risk of developing the disease was "responsible," he criticized The Wall Street Journal for classifying the gene as one causing Alzheimer's.

In fact, Tanzi said, APOE could simply be physically associated with another gene on another chromosome that acts to cause Alzheimer's.

"Clearly, the data is very strong--it's a breakthrough, a clear-cut risk factor," he said. "It doesn't mean the gene has anything to do with the disease.

While he said that Haines' statement that two copies of the gene greatly increases the risk of developing the disease was "responsible," he criticized The Wall Street Journal for classifying the gene as one causing Alzheimer's.

In fact, Tanzi said, APOE could simply be physically associated with another gene on another chromosome that acts to cause Alzheimer's.

"Clearly, the data is very strong--it's a breakthrough, a clear-cut risk factor," he said. "It doesn't mean the gene has anything to do with the disease.