Caring Currents

Another Alzheimer's Gene Identified

Last updated:

July 16, 2009
DNA rendering
Image by ynse used under the creative commons attribution share alike license.

Why do some people who have the "Alzheimer's gene," as the high-risk variant apolipoprotein ApoE4 is known, never develop the disease, while others who have a "safe" variant of the gene (ApoE3) still get Alzheimer's? Scientists don't yet know -- but the discovery of the DNA makeup of a new gene linked to apolipoprotein, called [TOMM40] (http://online.wsj.com/article/SB124744102025329841.html), brings them a step closer to figuring it out.

Apparently there are two types of mutations to TOMM40, a "long repeat" form and a "short repeat" form. The long and short refer to how many extra copies of a particular substance of DNA appear in the gene. People who carry the ApoE3 gene plus the long repeat form of TOMM40 develop Alzheimer's some seven years earlier -- at about age 70 -- than do people with ApoE3 and "short repeat" TOMM40.

The finding needs to be verified with more research, and then scientists will have to figure out what to do with this information. In theory, it can lead to better genetic testing and the development of precisely targeted drugs.

Meanwhile this news seems like a good opportunity to point out some basic facts about genetics and Alzheimer's:

1. There's no genetic test that will tell you if you're going to develop Alzheimer's.

Despite encouraging work to identify probable cases of Alzheimer's, including screening tests that have accuracy in the 90 percent range, current tests can't definitively predict who will develop the condition.

2. About three-fourths of Alzheimer's cases occur in people without a family history of the disease.

Knowing your genetic makeup can be informative, especially as researchers learn more about what it all means, but so far genes aren't the biggest predictor of who will develop Alzheimer's.

3. It's useful to understand what's meant by the "Alzheimer's gene."

It's been about 15 years since the apolipoprotein gene was discovered on chromosome 19 and made the term "ApoE4" a household acronym for those in the Alzheimer's world. Apolipoprotein has three variants:

  • ApoE3, the most common type, appears to have little effect on whether you develop Alzheimer's.
  • ApoE2 , the least common type, appears to have a protective effect against Alzheimer's
  • ApoE4 is the type that appears to increase your odds of developing Alzheimer's. It occurs in 25 to 30 percent of the population, according to the National Institutes of Health. Everyone inherits two ApoE genes, one from each parent. People with two ApoE4 genes (one from each parent) appear to have the very highest risk of developing Alzheimer's.

5. And yet, ApoE4 isn't destiny.

Not all people with the ApoE4 gene variant go on to develop the disease; only 40 percent do. In fact, you can have two copies of ApoE4 and still not develop Alzheimer's. And many people without ApoE4 still get Alzheimer's. Obviously there are other factors -- and other genes, like TOMM40 -- at play (including such risk factors already identified: heart health, obesity, depression, and so on).

6. All of the above applies to late-onset Alzheimer's.

Most cases of Alzheimer's are late-onset (occurring after age 60). Three other genes have been linked to a different type, early-onset Alzheimer's, which strikes between ages 30 and 60, and often runs in families. These genes are amyloid precursor protein (APP), presenilin 1 (PSEN-1), and presenilin 2 (PSEN-2).

But even these genes, which are strongly linked to early Alzheimer's, aren't completely understood yet. Many people are developing early Alzheimer's who don't have any of these genes.

Early-onset Alzheimer's is considered rare, accounting for only 5 percent of all cases. But the total number of cases seems to be rising. Which makes any step forward about unraveling the mysteries of Alzheimer's that are coiled within our genes a welcome step indeed.