Alzheimer's genes: Are you at risk?

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Alzheimer's genes: Are you at risk?

Alzheimer's genes are genes that make you more likely to develop Alzheimer's disease. Genes control the function of every cell in your body. Some genes determine basic characteristics, such as the color of your eyes and hair. Other genes can make you more likely to develop certain diseases — including Alzheimer's.

Researchers have identified several Alzheimer's genes — genes that are associated with Alzheimer's disease. But genetic risk factors are just one part of the Alzheimer's story, a complex narrative that scientists continue to try to unravel.

Most common late-onset Alzheimer's gene

While some rare forms of Alzheimer's occur before the age of 65, the most common variety of Alzheimer's usually begins after the age of 65. The most common gene associated with this late-onset Alzheimer's is called apolipoprotein E (APOE).

APOE has three common forms:

  • APOE e2 — the least common — appears to reduce the risk of Alzheimer's.
  • APOE e4 — a little more common — appears to increase the risk of Alzheimer's.
  • APOE e3 — the most common — doesn't seem to affect the risk of Alzheimer's in either direction.

Genes aren't only factor
Because you inherit one APOE gene from your mother and another from your father, you have two copies of APOE gene — for example, one APOE e3 gene and one APOE e4 gene. Having at least one APOE e4 gene increases your risk of developing Alzheimer's. And if you have two APOE e4 genes, your risk is even higher.

But not everyone who has an APOE e4 gene — or even two APOE e4 genes — develops Alzheimer's. And the disease occurs in many people who have no APOE e4 gene. This indicates that the APOE e4 gene affects risk, but it is not a causative gene. Other genetic and environmental factors are likely involved in the development of Alzheimer's.

Other late-onset genes

As research on the genetics of Alzheimer's progresses, researchers are uncovering links between late-onset Alzheimer's and a number of other genes. Several examples include:

  • SORL1. Some variations of SORL1 appear to increase the production of amyloid-beta fragments, which form structures called amyloid plaques in the brain. These plaques are one of the hallmarks of Alzheimer's disease.
  • CLU. This gene helps regulate the clearance of amyloid-beta from the brain. The association of this gene with Alzheimer's reinforces the theory that an imbalance in the production and clearance of amyloid beta is central to the development of Alzheimer's.
  • CR1. A deficiency of the protein this gene produces may contribute to chronic inflammation in the brain. Inflammation is another potential contributing factor to the development of Alzheimer's.
  • PICALM. This gene is linked to the process by which brain nerve cells (neurons) communicate with each other. Smooth communication between neurons is important to the proper functioning of neurons and to the formation of memory.

Researchers hope that discovery of these genes will help them learn more about the basic mechanisms of Alzheimer's and consequently, ways to treat and prevent the disease. But similar to APOE, these genes are risk factors, not direct causes. In other words, having a variation of one of these genes may increase your risk of Alzheimer's. But knowing whether you have such a variation doesn't help predict whether you will ultimately develop Alzheimer's.

Early-onset Alzheimer's

A very small percentage of the people who develop Alzheimer's disease have the early-onset variety, which is classified as beginning before the age of 65.

Scientists have identified three genes in which mutations cause early-onset Alzheimer's. If you inherit one of these mutated genes from either parent, you almost certainly will experience Alzheimer's symptoms before the age of 65. The genes involved are:

  • Amyloid precursor protein (APP)
  • Presenilin 1 (PSEN1)
  • Presenilin 2 (PSEN2)

Mutations of these genes cause the production of excessive amounts of a toxic protein fragment called amyloid-beta peptide. As these fragments stick together and deposit in the brain as amyloid plaques — and somehow induce changes in another brain protein called tau — the brain cells start dying and the signs and symptoms of Alzheimer's begin.

However, some people who have early-onset Alzheimer's don't have mutations in any of these three genes. That suggests that this early onset form of Alzheimer's disease is linked to other genetic mutations that haven't been identified yet.

Genetic testing

Most experts don't recommend genetic testing for late-onset Alzheimer's. In some instances of early-onset Alzheimer's, however, genetic testing may be appropriate.

In the case of APOE, knowing whether you have the e4 variety really doesn't tell you much. Although many people with APOE e4 develop Alzheimer's, many don't. Conversely, some people with no APOE e4 genes get Alzheimer's. Most clinicians discourage testing for the APOE genotype, as the results are often difficult to interpret.

Testing for the mutant genes that have been linked to early-onset Alzheimer's — APP, PSEN1 and PSEN2 — may provide more certain results and have implications for current and future therapeutic drug trials. But it's also important to weigh the emotional consequences of having that information. There also may be eligibility implications for certain forms of insurance, such as disability, long term care and life insurance.

Even without genetic testing, doctors can diagnose Alzheimer's with 90 percent accuracy.

Researchers and genes

Researchers suspect that there are dozens more genes that affect Alzheimer's disease risk that have not yet been identified or confirmed. Scientists study the genetics of Alzheimer's disease because understanding the basis of a disease may provide clues about how to combat it. Such information may prove vital in the development of new ways to treat, or even prevent, Alzheimer's disease in the future.

The Alzheimer's Disease Genetics Study, sponsored by the National Institute on Aging, is examining genetic information from families that have at least two siblings who have developed Alzheimer's after the age of 60. If your family is interested in participating in this study, visit the web site for the National Cell Repository for Alzheimer's Disease (NCRAD).

Last Updated: 2010-08-05
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