The majority of AD cases are late-onset, usually developing after age 65. Late-onset AD has no known cause and shows no obvious inheritance pattern. However, in some families, clusters of cases are seen. Although a specific gene has not been identified as the cause of late-onset AD, genetic factors do appear to play a role in the development of this form of AD. Only one risk factor gene has been identified so far.
Researchers have identified an increased risk of developing late-onset AD related to the apolipoprotein E 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, and APOE e4.
For John MacInnes, the beginnings of Alzheimer’s disease were startling. The retired executive and former pastor in Bloomfield Hills, Mich., first realized something was wrong as he was delivering a PowerPoint presentation to a community group. “Then in mid-sentence, I had problems,” he says. “I had a well-rehearsed script in front of me, but I couldn’t get the words right, couldn’t get them out. That kind of shook me up.”
Memory loss and impaired thinking are hallmark symptoms of this disease...
People inherit one APOE allele from each parent. Having one or two copies of the e4 allele increases a person's risk of getting AD. That is, having the e4 allele is a risk factor for AD, but it does not mean that AD 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 AD. The rarer e2 allele appears to be associated with a lower risk of AD. The exact degree of risk of AD 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 AD.
Scientists are looking for genetic risk factors for late-onset AD on other chromosomes as well. They think that additional risk factor genes may lie on regions of chromosomes 9, 10, and 12.
The National Institute on Aging (NIA) has launched a major study to discover remaining genetic risk factors for late-onset AD. Geneticists from the NIA's Alzheimer's Disease Centers are working to collect genetic samples from families affected by multiple cases of late-onset AD. Researchers are seeking large families with two or more living relatives with late-onset AD. Families interested in participating in this study can contact the National Cell Repository for Alzheimer's Disease at 1-800-526-2839. Information may also be requested through their website, http://ncrad.iu.edu.