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Genetics and Alzheimer's Disease |
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Is Alzheimer's disease hereditary? Scientists recognize two types of Alzheimer's disease: familial (multiple family members are affected) and sporadic (one or a few individuals in a family have the disease). Experts further distinguish between early-onset Alzheimer's, which affects people between the ages of 30 and 65, and late-onset disease, which is diagnosed in people who are at least 65. Early-onset, familial Alzheimer's, which accounts for only about 5 percent of cases, is strongly hereditary. Late-onset Alzheimer's, the common form, has a subtler and less clearly understood inheritance pattern. In particular families, Alzheimer's may occur in patterns that blur these distinctions-late-onset, sporadic disease may sometimes mimic the usual pattern of familial disease by striking several individuals in a family, and familial disease may strike only one or two individuals and thus appear sporadic. The average worldwide lifetime risk of developing any type of Alzheimer's is about 5 percent by age 65, 10 to 15 percent by age 75, and 20 to 40 percent by age 85. Individuals who have a parent with Alzheimer's have about twice the average risk-among 65-year-olds with an affected parent, about 10 percent will develop Alzheimer's. Having a brother or sister with the disease also doubles the risk. The likelihood of developing the disease continues to increase as the number of affected relatives rises, and having more than one affected sibling appears to cause the greatest increase in risk. This increased risk occurs because children and parents may share certain genes, the basic units of heredity that provide a blueprint for many biological and behavioral characteristics. The influence of a gene may be large or small. Certain alleles (forms) of genes are "deterministic"-having that form of the gene virtually guarantees a certain outcome. Other forms are "susceptibility" or "risk" genes-they raise the likelihood of a particular outcome but do not ensure it. What genes influence the risk of developing Alzheimer's? Scientists have so far identified several genes that influence the risk of developing Alzheimer's-one is associated with late-onset disease and three with early-onset, familial cases. The late-onset Alzheimer gene, which codes a cholesterol-processing protein called apolipoprotein E (ApoE), is a susceptibility gene that occurs in three different alleles (forms)-ApoE-e4, ApoE-e3, and ApoE-e2. Everyone inherits one form of ApoE from each parent. ApoE-e3 is the most common form and ApoE-e2 is the least common. Studies have shown that people with one copy of ApoE-e4 have an increased chance of developing Alzheimer's, and people who inherit two are at even higher risk. However, not everyone with two copies develops Alzheimer's, and many people with the disease have no ApoE-e4 at all. Experts believe that there are several other unidentified genes that also influence the likelihood of developing late-onset Alzheimer's disease. Environmental factors may also be involved. Three genes that have been implicated in early-onset, familial Alzheimer's code proteins called presenilin 1, presenilin 2, and amyloid precursor protein (APP). The forms of these genes that lead to Alzheimer's are deterministic-virtually everyone who has these forms develops the disease. Each child of a parent who has an Alzheimer-related mutation (change) in one of these genes has a 50 percent chance-or 1 chance in 2-of inheriting the form that causes Alzheimer's disease. Are there tests that can determine whether I have any of the genes associated with an increased risk of Alzheimer's? Tests are available that can determine whether a person carries copies of ApoE-e4 or certain types of the early-onset, familial Alzheimer's genes. Most experts do not recommend testing for ApoE-e4 because ApoE status is not predictive. Having one or two copies of ApoE-e4 suggests an increased risk-but not a certainty-of developing Alzheimer's, and lacking ApoE-e4 does not protect against it. For a person with symptoms of dementia, ApoE testing may offer an additional piece of evidence that the dementia is due to Alzheimer's. But in most situations, an Alzheimer diagnosis by a skilled clinician approaches 90 percent accuracy without ApoE testing. Most experts regard ApoE testing as an acceptable part of clinical trials as long as participants give informed consent and understand the procedure's purpose and limitations thoroughly. There is professional consensus that testing may make more sense for people in families affected by early-onset, familial Alzheimer's because these types of Alzheimer's strike virtually every person who carries one of the genes and have a 50 percent chance of affecting future children. Tests are available that can detect early-onset mutations in genes for presenilin 1, presenilin 2, and amyloid precursor protein. Almost every early-onset Alzheimer family identified has a unique genetic change. Experts commonly recommend that the complex analysis involved in characterizing such one-of-a-kind gene mutations be carried out at a major academic center and that individuals receive genetic counseling as part of the testing process. Genetic counselors help people explore emotional and legal implications as well as scientific and technical issues before testing proceeds; after testing is completed, they explain and interpret results and help people accept the outcome.
This fact sheet, prepared by the National office of the Alzheimer's Association, is provided for your information only and does not represent a recommendation for any course of action by the Alzheimer's Association.
Last updated: September 8, 2000
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