A local research team has identified a second gene that appears to put people at greater risk for developing Alzheimer’s disease, opening the door for early diagnosis and treatment.
The study of DNA from 1,400 people, including those identified at autopsy as having the disease, is the largest genetic study ever done on Alzheimer’s, a brain-withering illness that affects nearly 5 million people in the U.S., including 78,000 in Arizona, and is projected to afflict three times that many by 2050.
The results appear today in the journal Neuron.
Local researchers, led by the Translational Genomics Research Institute (TGen), the Banner Alzheimer’s Institute and Kronos Science Laboratory, looked at 500,000 genetic markers to discover a common gene, called GAB2.
Further study revealed that the gene, depending on its variant, may protect brain cells from the tangles that characterize the disease. People with variants of both GAB2 and another gene associated with Alzheimer’s, called ApoE4, are believed to be at increased risk.
“The gene is quite important in its diagnostic potential,” said Dr. Dietrich Stephan, director of TGen’s Neurogenomics Division and a lead author of the study. “By layering in GAB2, we really refine our ability to define risk.”
The $5 million study, funded by Kronos, the state and the National Institutes of Health, could aid development of a genetic test to find out if you’re likely to develop the disease, decades before the first symptoms.
That kind of diagnoses could be available within a year for Alzheimer’s and other diseases, Stephan said, but must be coupled with counseling and preventive treatment.
“All of this has got to start by empowering them and not scaring them,” he said.
Already researchers have found evidence that healthy, low-cholesterol diets together with physical and mental exercise can reduce the risk or delay onset of Alzheimer’s and related dementias.
Because age is the greatest risk factor — roughly half of those 85 and older have some type of dementia — just delaying onset of symptoms by five to 10 years would dramatically reduce the number of people afflicted.
“If we start doing this type of pre-symptomatic risk-assessment now, give people a window in which to do something about it, we could reduce the onset by 50 percent,” Stephan said.
“We could save 8 million people in this country alone from getting Alzheimer’s disease.”
The gene discovery, together with the data set, also will allow future studies to be more narrowly focused.
“We’re excited about this finding, because we think it ushers in this new era of genetic research,” said Dr. Eric Reiman, a lead study author and executive director of the Banner Alzheimer’s Institute.
“Now, instead of having people do studies of their favorite genes, they’ll go to our database and see if they’re on the right track,” Reiman said. “This is a hugely valuable service.”
The data will be offered publicly to other researchers, an unusual step in a rather parochial field defined by intellectual property rights. Though GAB2 is believed to be the key finding, other discoveries could come from the DNA data.
“We’ve exhaustively mined that data set,” Stephan said. “So future analyses may find more subtle effects that contribute to Alzheimer’s disease.”
Study participants also included Mayo Clinic in Scottsdale, Sun Health Research Institute in Sun City and the Netherlands Brain Bank.
Once the scientists identified the GAB2 gene in three separate groups, they found that it was especially active in the diseased brains.
That led them to wonder if the protein produced by healthy GAB2 acted as a barrier to tangles, a hallmark of Alzheimer’s which, together with the development of plaque, eventually kills brain cells.
Indeed, when GAB2 was turned off, it increased the molecular process that leads to tangles.
Family members of those with dementia often wonder if they might be next. To know their risk, and be able to do something about it, would be a huge breakthrough, scientists and families say.
Clotele Armstrong’s children worry, too. Recently, her daughter told her: “Mom, every time I can’t remember something, I think, oh my gosh. Is it starting?”
Armstrong’s husband, Wesley, is part of a study at the Banner Alzheimer’s Institute to see if lavender can help induce a deeper sleep that might strengthen his brain. He began showing symptoms of dementia about six years ago, and violent outbursts led them to the institute, which opened last summer.
“It was like a godsend to us,” Clotele said. “It’s a disease that takes away everything that was joyful in your life... And it’s a very long goodbye,” she said.
It’s made a bit easier thanks to support from family, friends, a part-time caregiver and the institute.
“Early on I made some very bravado statements about how I could do this. It was foolish,” she said. “You can’t do it alone.”
The Alzheimer’s Research Registry is designed to match people with study opportunities. The registry is open to English-speaking adults, with or without memory problems, who are at least 50 years old.
For more information or to register, call (602) 239-6500, go to www.registry.azalz.org.