2. AD Risk Factors We Can’t Control

Age is the most important known risk factor for AD. The risk of developing the disease doubles every 5 years over age 65. Several studies estimate that up to half the people older than 85 have AD. These facts are significant because of the growing number of people 65 and older. More than 34 million Americans are now 65 or older. Even more significant, the group with the highest risk of AD—those older than 85—is the fastest growing population group in the country.

Genetics is the other known AD risk factor that a person can’t control. Scientists have found genetic links to the two forms of AD. Early-onset AD is a very rare form of the disease that can occur in people between the ages of 30 and 65. In the 1980s and early 1990s, researchers found that mutations (or changes) in certain genes on three chromosomes cause early-onset AD. If a parent has any of these genetic mutations, his or her child has a 50-50 chance of inheriting the mutant gene and developing early-onset AD.

Late-onset AD, the more common form, develops after age 65. In 1992, researchers found that certain forms of the apolipoprotein E (APOE) gene can influence AD risk:

• APOE ε2, a rarely occurring form, may provide some protection;
• APOE ε3, the most common form, plays a neutral role; and
• APOE ε4, which is found in about 40 percent of people with AD; APOE ε4 lowers the age of onset and thus increases risk. (Having this gene form does not mean that a person will definitely develop AD; it only increases risk. Many people who develop AD do not have the APOE ε4 form.)

Researchers are now intensively searching for other risk factor genes that may be linked to late-onset AD. Discovering these genes is essential for understanding the very early biological steps leading to AD and for pinpointing targets for drug development and other prevention or treatment strategies. It’s also critical for developing better ways to identify people at risk and determining how AD risk factor genes may interact with other genes or with lifestyle or environmental factors to affect AD risk in any one individual.

In 2003, the NIA announced a major expansion of AD genetics research efforts. The AD Genetics Study is collecting genetic material from individuals in families with two or more living brothers or sisters who have late-onset AD. This valuable resource will allow geneticists to speed up the discovery of additional AD risk factor genes.

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