Alzheimer's: Is it in your genes?

What role does genetics play in developing Alzheimer's? Are you at risk?

You've got your mother's curly hair and your dad's green eyes. These traits came to you through your chromosomes — a legacy from your parents. But what else have you inherited? Is the key to Alzheimer's hidden in your genes?

What are chromosomes?

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Chromosomes and genes

Each cell in your body contains 23 pairs of chromosomes. In each pair of chromosomes, one is from your mother and the other from your father. Each chromosome consists of DNA spirals, divided into short sections called genes.

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.

Genes that cause Alzheimer's

Researchers have identified three genes that cause early-onset Alzheimer's. If you inherit one of these mutated genes from either parent, you almost certainly will start having Alzheimer's symptoms before the age of 65.

Luckily, early-onset Alzheimer's is very rare. Only about 200 families in the world carry the gene mutations that cause it. The genes involved are:

Amyloid precursor protein (APP)
Presenilin 1 (PS1)
Presenilin 2 (PS2)

These abnormal genes cause the production of excessive amounts of a toxic protein fragment called amyloid-beta peptide. As these fragments proliferate in the brain, the brain cells start dying and the signs and symptoms of Alzheimer's begin.

APOE and its variations

A different gene, called apolipoprotein E (APOE), has been linked to the development of the much more common form of Alzheimer's — late-onset Alzheimer's — which typically begins after the age of 65.

While APOE doesn't directly cause late-onset Alzheimer's, one variety increases your risk of Alzheimer's, and another variety may actually reduce your risk. APOE has three common forms:

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

APOE combinations

Because you inherit one APOE gene from your mother and another from your father, you may have two different types of APOE genes — for example, one APOE e3 gene and one APOE e4 gene. Up to 50 percent of the people who have Alzheimer's have at least one APOE e4 gene. And people who have two APOE e4 genes tend to have an even higher risk of developing Alzheimer's.

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 copies of the APOE e4 gene. This suggests other factors are involved in the development of Alzheimer's.

New gene linked to Alzheimer's

Study results released in January 2007 showed a link between late-onset Alzheimer's and a new gene known as SORL1. This is the first gene, other than APOE, to be linked to the most common form of Alzheimer's. Some variations of SORL1 appear to increase the production of amyloid-beta fragments, which form structures called plaques inside the brain. Plaques are one of the hallmarks of Alzheimer's disease.

Researchers believe that these SORL1 variations may modestly increase the risk of developing Alzheimer's disease.

Other genes

Scientists are studying several other genes that might be connected to Alzheimer's:

Ubiquilin 1 (UBQLN1). This gene appears to interact with the presenilin genes (PS1 and PS2) and may play a role in the breakdown of proteins in the brain.
Angiotensin-converting enzyme (ACE). One form of this gene may be linked to a higher risk of Alzheimer's, but study results have been mixed.
Apolipoprotein A1 (APOA1). Like APOE, this gene controls production of a protein that carries cholesterol in the blood. It is being investigated because of the apparent link between high cholesterol and the risk of Alzheimer's.

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, some don't. Conversely, some people with no APOE e4 genes get Alzheimer's.

While testing for the mutant genes that have been linked to early-onset Alzheimer's — APP, PS1 and PS2 — may provide more certain results, the emotional consequences of having that information might be devastating. And the information could result in employment or health insurance discrimination.

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

Researchers and genes

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, call 800-526-2839.