The Role of ApoE in Sporadic AD

Some confusion surrounds sporadic AD, which is far more common than FAD. Sporadic AD is related to the apoE gene found on chromosome 19.

ApoE comes in three different forms or alleles. People inherit one allele (apoE2, apoE3, or apoE4) on the apoE gene on chromosome 19 from each parent. People with both apoE3 and apoE4 alleles (E3/4) are affected by both alleles.

Having one or two copies of the E4 allele may increase a person’s risk of getting AD. That is, having the E4 allele of the apoE gene is a risk factor for AD. But, it does not mean that AD is inevitable. Having one or two E4 alleles of the apoE gene increases risk of AD, but not to 100 percent. Some people with two copies of the E4 allele (the highest risk group) have not developed the disease, and others with no E4’s have. Scientists have yet to determine the exact degree of risk of AD for any given person based on apoE status.

Dr. Allen Roses and his colleagues at the Duke University Alzheimer’s Disease Center in Durham, North Carolina, studied 72 families to see how a person’s apoE status relates to age of onset for AD. Participants included 158 people with late-onset, sporadic AD (affected) and 220 without (unaffected). At age 70, 50 percent of those with E4/4 remained unaffected. At the same age, 72 percent of those with E3/4 and 94 percent of those with E2/4 and E3/3 remained unaffected. Also at age 70, 100 percent of those with E2/3 remained unaffected.

ApoE Testing — A blood test is available to assess apoE status because the allele also is associated with heart disease, which has been well studied. However, this blood “test” cannot tell people whether they will develop the disease. Instead of a “yes” or “no” answer, the best information one can get from genetic assessment for apoE is “maybe” or “maybe not.”

Many questions remain at this time about the usefulness of apoE testing in non-research settings. Some researchers predict that the best use of apoE testing will be as part of a complete patient assessment, rather than as a stand-alone test for AD.

Source: Connection Magazine [Volume 5(1), Winter/Spring 1996]

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