Genetic Considerations

AD is not caused by a single gene. The genetic contributions to the disease are complex because more than one gene mutation can cause AD, and genes on multiple chromosomes are involved. There are two basic types of AD from a genetic standpoint: familial and sporadic (associated with late-onset disease). Familial AD (FAD) is a rare form of AD that has an early onset before age 65 and affects less than 10% of AD patients. FAD is caused by gene mutations on chromosomes 1, 14, and 21 and has an autosomal dominant inheritance pattern. Therefore, if one of these mutated genes is inherited from a parent, the person will almost always develop early-onset AD.

The majority of AD cases are late-onset (developing after age 65), have no known cause, and show no clear inheritance pattern. Late onset AD is linked with the apolipoprotein E (ApoE) gene on chromosome 19. It is involved with making ApoE, a substance that transports cholesterol in the bloodstream. The ApoE e4 gene is considered a risk-factor gene for AD and appears to influence the age of onset of the disease. The ApoE gene comes in several different alleles, but the three alleles that occur most frequently are ApoE e2, ApoE e3, and ApoE e4. No one really understands the degree of risk of AD based on ApoE status. Scientists continue to search for genetic risk factors for late-onset AD on regions of chromosomes 9, 10, and 12 as well as chromosome 19.

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