AD Risk Factors We Can’t Control

Age

Age is the most important known risk factor for AD. The risk of developing the disease doubles every 5 years after age 65. Several studies estimate that up to half of all people older than 85 have AD. These facts are significant because of the growing number of people 65 and older. A 2005 Census report estimates that the number of Americans 65 and older will more than double to about 72 million by 2030. Even more significant, the group with the highest risk of AD—those older than 85—is the fastest growing age group in the United States.

Genetics

Genetic risk is another factor that a person can’t control. Scientists have found genetic links to the two forms of AD—early-onset and late-onset.

Early-onset AD is a rare form of the disease, affecting only about 5 percent of all people who have AD. It develops in people ages 30 to 60. In the 1980s and early 1990s, researchers found that mutations (permanent abnormal changes) in certain genes cause most cases of early-onset AD. If a parent has any of these genetic mutations, his or her child has a 50-50 chance of inheriting the mutated gene and developing early-onset AD.

Late-onset AD, the much more common form of the disease, develops after age 60. In 1992, researchers found that three forms, or alleles (ε), of a gene called apolipoprotein E (APOE) can influence the risk of late-onset AD:

• APOE ε2, a rarely occurring form, may provide some protection against AD.
• APOE ε3, the most common form, plays a neutral role, neither increasing nor decreasing risk.
• APOE ε4, which occurs in about 40 percent of all people who develop late-onset AD and is present in about 25 to 30 percent of the population, increases risk by lowering the age of onset. Having this allele does not mean that a person will definitely develop AD; it only increases risk. Many people who develop AD do not have an APOE ε4 allele.

Researchers think that at least half a dozen other risk-factor genes exist for late-onset AD and are intensively searching for them. In 2007, they found another likely risk-factor gene called SORL1. When this gene is active at low levels or in an abnormal form, levels of harmful beta-amyloid increase in the brain. Beta-amyloid is a component of amyloid plaques, one of the hallmarks of AD. Interestingly, the SORL1 gene also was identified as a risk-factor gene for certain aspects of cognitive decline, suggesting that cognitive decline and AD may share at least one predisposing genetic factor.

Finding AD risk-factor genes is essential for understanding the very early biological steps that lead to the vast majority of AD cases and for developing drugs and other prevention and treatment strategies. Finding these genes also will help scientists develop better ways to identify people at risk of AD and determine how the genes may interact with other genes or with lifestyle or environmental factors to affect an individual’s AD risk.

<< Back | Next >>