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More Details on the Genetics of Alzheimer's Disease

Alzheimer's and Genes: The Genetics of Alzheimer's Disease

Diseases such as cystic fibrosis, muscular dystrophy, and Huntington's disease are single-gene disorders. If a person inherits the gene that causes one of these disorders, he or she will usually get the disease. On the other hand, a single gene does not cause Alzheimer's disease (AD). More than one gene mutation can cause Alzheimer's disease, and genes on multiple chromosomes are involved.
The two basic types of Alzheimer's disease are familial and sporadic. Familial Alzheimer's disease (FAD) is a rare form of Alzheimer's disease, affecting less than 10% of patients with Alzheimer's. All cases of FAD are early-onset, meaning the disease develops before age 65. It is caused by gene mutations on chromosomes 1, 14, and 21. Even if only one of these mutated genes is inherited from a parent, the person will almost always develop early-onset Alzheimer's disease. This inheritance pattern is referred to as autosomal dominant inheritance. In other words, all offspring in the same generation have a 50/50 chance of developing FAD if one of their parents had it.

Alzheimer's and Genes in Late-Onset Alzheimer's Disease

The majority of Alzheimer's disease cases are late-onset, meaning the disease develops after age 65. Late-onset Alzheimer's disease has no known cause and shows no obvious inheritance pattern. However, in some families, clusters of cases are seen. Although no specific gene has been identified as the cause of late-onset Alzheimer's disease, genetic factors do appear to play a role in the development of this form of Alzheimer's disease. Only one risk factor gene has been identified so far.
Researchers have identified an increased risk of developing late-onset Alzheimer's disease related to the apolipoprotein E (APOE) gene found on chromosome 19. This gene codes for a protein that helps carry cholesterol in the bloodstream. The APOE gene comes in several different forms, or alleles, but three occur most frequently:
  • APOE e2
  • APOE e3
  • APOE e4.
People inherit one APOE allele from each parent. Having one or two copies of the e4 allele increases a person's risk of getting Alzheimer's disease. That is, having the e4 allele is a risk factor for Alzheimer's disease, but it does not mean that Alzheimer's disease is certain. Some people with two copies of the e4 allele (the highest risk group) do not develop clinical signs of Alzheimer's disease, while others with no e4s do. The e3 allele is the most common form found in the general population and may play a neutral role in Alzheimer's disease. The e2 allele, which is more rare, appears to be associated with a lower risk of AD. The exact degree of risk of Alzheimer's disease for any given person cannot be determined based on APOE status. Therefore, the APOE e4 gene is called a risk factor gene for late-onset Alzheimer's disease.
Scientists are looking for genetic risk factors for late-onset Alzheimer's disease on other chromosomes as well. They think that additional risk factor genes may lie on regions of chromosomes 9, 10, and 12.
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