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Published on: January 28, 2012
by Dementia Today:
Many people worry about getting Alzheimer’s, particularly if a parent or sibling suffers from the disease. But is it a good idea to get a genetic test to see if you carry genes that increase your risk for the disease?
Scientists have learned much about the genetics of Alzheimer’s in recent years. And increasingly, companies are offering genetic tests to consumers that allow them to assess their risk for the disease. Still, there is much that needs to be learned about Alzheimer’s genes and the underlying causes of the disease. Determining who will ultimately get Alzheimer’s is impossible in most cases, and treatments for the disease remain limited.
Now, two professional medical organizations, the American College of Medical Genetics and the National Society of Genetic Counselors, have issued guidelines for genetic testing of Alzheimer’s. The guidelines, published in the journal Genetics in Medicine, are aimed at clarifying the different forms of Alzheimer’s disease and helping doctors and patients better determine who might benefit from genetic tests for the disease.
The science remains imperfect and more research needs to be done, but experts are learning more about the role of genes in Alzheimer’s disease. Over all, the lifetime risk of getting Alzheimer’s is estimated at between 10 and 12 percent. So the average person in the general population living to 75 or 80 has about a one in 10 chance of getting Alzheimer’s. Having a mother, father, brother, sister or other close relative with the disease increases that risk two-fold.
The genetics of Alzheimer’s, however, are complex. Alzheimer’s comes in various forms, and some types are more likely to be influenced by genes than others. So-called early-onset familial Alzheimer’s typically strikes before age 60 and clearly runs in families.
It has been linked to specific genes, and inheriting a mutated gene from either parent – a parent has a 50 percent chance of passing it on to a child — almost always causes the disease to arise.
But the far more common late-onset Alzheimer’s, which occurs after age 60 to 65 and grows increasingly common in people in their 70s and 80s and older, is only partly influenced by genetics. It clusters in families only 15 to 25 percent of the time, and is generally referred to as sporadic Alzheimer’s. In these cases, having a mother or father, brother or sister, aunt or uncle, grandparent or other close relative with Alzheimer’s increases your risk for the disease. But a family history by no means guarantees that you will get it.
Sporadic Alzheimer’s can also arise when no known family members have the disease. Sporadic Alzheimer’s can occur with early-onset disease, but most cases occur as the late-onset form. In fact, sporadic Alzheimer’s accounts for the vast majority of cases.
So what causes these different forms of Alzheimer’s? Genetics explains only part of the picture.
Scientists have identified several gene mutations that, if you inherit one or two copies from your mother or father, almost always cause Alzheimer’s. These genes, called presenilin 1, presenilin 2 and apolipoprotein precursor protein, or APP, cause the early-onset familial form of the disease that arises in people in their 30s, 40s or 50s. With familial form of Alzheimer’s, there usually will be many parents, siblings, cousins and others afflicted with dementia. If you carry one of these gene mutations, it is a good predictor that you will get Alzheimer’s. But these genes are rare (scientists continue to look for others) and account for only 1 to 5 percent of total Alzheimer’s cases.
Far more common is the gene known as APOE-E4. This gene increases your risk of developing Alzheimer’s, but does not cause the disease. That is, if you carry the E4 form of the APOE gene (the APOE gene helps the body process cholesterol), you are at increased risk of getting Alzheimer’s, but you won’t necessarily get it.
It’s possible to inherit one or two copies of APOE-E4, from one or both parents. Those who carry only one copy have a two- to three-fold increased risk compared to the general population, though the risk is uncertain and experts can’t assign a definitive number to it. In people who carry two copies of APOE-E4, the overall risk is increased two- to 10-fold. Some studies suggest that having the APOE-E4 gene may cause symptoms like memory loss to appear at an earlier age than if you didn’t carry the gene. And some forms of APOE, like APOE-E2, may actually help protect against Alzheimer’s. In addition to APOE-E4, other genes that increase risk have been identified, and more may be found, though APOE-E4 seems to be most important.
So the genetics of Alzheimer’s are complex. Genes and family history may play varying roles in the many forms of Alzheimer’s: early-onset or late-onset, and inherited, familial and sporadic. Given the imperfect state of the science, professional genetic counselors have various recommendations for those considering genetic testing. Among the recommendations of the professional groups:
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