Mayo Clinic Health Library

Alzheimer's genes: Are you at risk?

Updated: 02-09-2013

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 disease.

Researchers have identified several genes that are associated with Alzheimer's disease. However, genetic risk factors are just one part of the Alzheimer's disease story.

Most common late-onset Alzheimer's gene

Although a rare form of Alzheimer's disease occurs before age 65 (early-onset Alzheimer's disease), the most common variety of Alzheimer's disease usually begins after age 65 (late-onset Alzheimer's disease). The most common gene associated with late-onset Alzheimer's disease 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.

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

Not everyone who has one or two APOE e4 genes develops Alzheimer's disease. The disease occurs in many people who have no APOE e4 gene, suggesting that the APOE e4 gene affects risk but is not a cause. Other genetic and environmental factors likely are involved in the development of Alzheimer's disease.

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 on chromosome 11 appear to be associated with Alzheimer's disease.
  • CLU. This gene helps regulate the clearance of amyloid-beta from the brain. Research supports the theory that an imbalance in the production and clearance of amyloid-beta is central to the development of Alzheimer's disease.
  • CR1. A deficiency of the protein this gene produces may contribute to chronic inflammation in the brain. Inflammation is another possible factor in the development of Alzheimer's disease.
  • PICALM. This gene is linked to the process by which brain nerve cells (neurons) communicate with each other. Smooth communication between neurons is important for proper neuron function and memory formation.
  • TREM2. This recently identified gene is involved in the regulation of the brain's response to inflammation. Rare variants in this gene are associated with an increased risk of Alzheimer's disease.

Researchers seek to learn more about the basic mechanisms of Alzheimer's disease and, consequently, ways to treat and prevent the disease.

As with 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. However, knowing whether you have such a variation doesn't help predict whether you'll develop Alzheimer's.

Early-onset Alzheimer's

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

Scientists have identified three genes in which mutations cause early-onset Alzheimer's disease. If you inherit one of these mutated genes from either parent, you'll likely experience Alzheimer's symptoms before age 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 collect in the brain as amyloid plaques, the tau protein malfunctions. As the tau protein particles stick together and form neurofibrillary tangles, the brain cells die and the signs and symptoms of Alzheimer's disease develop.

However, some people who have early-onset Alzheimer's don't have mutations in 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 doesn't tell you whether you'll develop Alzheimer's. Although many people with APOE e4 develop Alzheimer's, many don't. Conversely, some people with no APOE e4 genes develop Alzheimer's. Most clinicians discourage testing for the APOE genotype because the results are 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.

Before being tested, it's important to weigh the emotional consequences of having that information. The results may affect your eligibility for certain forms of insurance, such as disability, long-term care and life insurance.

Doctors often can accurately diagnose Alzheimer's disease without genetic testing.

Researchers and genes

Researchers suspect that many more genes that haven't been identified yet affect Alzheimer's disease risk. 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 family members who have developed Alzheimer's after age 65. If your family is interested in participating in this study, visit the website for the National Cell Repository for Alzheimer's Disease.

Several other studies evaluate genetics of people with Alzheimer's disease and their family members.