Genes are a gateway to understanding disease, and Alzheimer’s is certainly no exception. In recent years, researchers have grown the list of known genes associated with the most common form of the condition, which affects memory and brain function the elderly. But the question is, How do these discoveries help patients?
This week, two groups reported in the journal Nature Genetics that they had identified five new genes linked to an increased risk of late-onset Alzheimer’s — doubling the total number of genes known to contribute to the risk of the neurological disorder. Researchers were particularly excited by the discoveries, because they implicated new biological pathways — such as inflammation, cholesterol and cell transport systems — that had been suspected to play a role in Alzheimer’s, but had never been confirmed to do so.
The findings uncover brand new targets for potential treatments for the disease, whether they may be drugs, behavioral changes or other therapies.
But as the list of known risk genes grows, doctors’ ability to act on the new information remains relatively stagnant. Knowing a patient’s genetic profile doesn’t change his or her prognosis nor does it change treatment options for Alzheimer’s patients — at least not yet.
So what should the 5.4 million current Alzheimer’s patients do with this stream of new information about their condition? Jennifer Williamson, a genetic counselor at Columbia University, one of the centers that contributed to the new gene discoveries, says it’s important for those concerned about Alzheimer’s to put the breakthroughs in perspective.
The identification of genes that may, when altered, confer more or less risk of developing the disease is only the first step in a long journey toward a test or a drug from which patients can benefit. Think of such genetic studies as reconnaissance missions — their goal is to survey the genetic landscape and identify possible weaknesses or areas of interest that set the DNA of Alzheimer’s patients apart from that of healthy controls.
These genetic variants will then have to be tested in larger populations to confirm how they contribute to processes like amyloid and tau formation or to symptoms of memory loss and cognitive decline — the hallmarks of Alzheimer’s. From there, scientists will have to scan thousands of chemical compounds for their ability to modify the effects of these genes, and more trials in patients will have to verify whether these effects have an impact on the symptoms or progression of the disease.
That’s a long but optimistic road toward scientific discovery, says Williamson, yet one on which many of the patients she counsels are willing to embark. “We take pains to be very honest with participants in our trials, and the people realize the enormity of the task at hand of trying to figure out this complicated illness,” she says. “A lot of my job is explaining to people the limitations of what we understand and what we don’t understand, and that there are a lot of incremental steps toward having a better understanding of this disease.”
Alzheimer’s gene trials can sometimes be a hard sell for potential volunteers, since they know up front that they will not benefit in any way from the knowledge emerging from the studies. “A lot of people understand that there isn’t much that they can do about their disease,” says Williamson, “so my job is to help them understand the facts and deal with their feelings of anxiety and worry, not just about their own health but about not wanting their children to be a in a position of caregiving when they become ill.”
The only action many patients can take is to join clinical trials in order to help researchers uncover the causes the disease, and help future generations. While that might seem like poor consolation, Williamson says that rather than frustrating patients, the string of innovations occurring in the field in recent years has actually galvanized them, as well as others who are at high risk for the disease.
Along with the identification of new genes, researchers have also discovered new ways of using imaging techniques, such as MRI, blood tests or spinal fluid tests, to predict who is more likely to progress to advanced stages of Alzheimer’s. These advances have inspired more people to volunteer for clinical trials. “They really have an interest in figuring this disease out,” says Williamson. “They realize they can be part of the solution, and that we can’t understand this disease without having more patients participate in studies.”
And the more people volunteer, she says, the more researchers can learn and eventually, someday repay their contribution by developing treatments that may help future generations stop the disease in its tracks.