July 30, 1998 Scientists at the Johns Hopkins School of Public Health have discovered that one of three normal variants of a gene called apolipoprotein-E (APOE) can be used to predict when a person will get Alzheimer's disease, if that person is predisposed to the disorder in the first place.
The study showed that the E-4 variant (or allele) of the APOE gene influenced the timing of the onset of Alzheimer's in about half of the population. The study appeared in the August 19 issue of Nature Genetics.
Senior author John C.S. Breitner, MD, professor and chair, Mental Hygiene, the Johns Hopkins School of Public Health, said, "About half the population will eventually get Alzheimer's, but we don't yet know how to distinguish those who will from those who won't. For the person who is predisposed for the disease, however, we have found that the number of E-4 genes he or she has inherited can tell us roughly how old that person will be when the disease strikes. By furthering our ability to predict how vulnerable a person is to Alzheimer's, these findings have implications for identifying lifestyle choices that may be protective against the disease."
The investigators administered a battery of standardized neuropsychological tests to a population of 4,932 elderly persons and then gave full clinical exams to those who were suffering from dementia, in order to determine the true cases of Alzheimer's. The authors then looked for relationships between the incidence of the disease and the presence or absence of the different variants of APOE.
In that half of the population predisposed for Alzheimer's, those who inherited two E4 alleles (one from each parent) experienced onset by age 80 to 85; those who inherited a single E4 allele from one parent developed the disorder by age 90 to 95. Those who inherited no E4 alleles got Alzheimer's by age 95 to 100, if at all. People in the half of the population not predisposed to the disorder did not develop Alzheimer's before age 100, no matter how many E-4 genes they had inherited.
Past studies have suggested that between 50 and 75 percent of a person's risk of developing Alzheimer's is genetically determined, and scientists have known for some time that the action of the APOE gene, which is involved in cholesterol transport, was somehow associated with the development of late-onset Alzheimer's.
Dr. Breitner, however, was quick to point out that inheritance was not the whole story. His group has also studied identical twins and siblings of families who were at high risk for the disease and found instances in which one twin developed Alzheimer's while the other didn't. "These findings in twins," said Dr. Breitner, "tell us that inheritance does not equal fate, and that other factors must be at work that delay, modify, or interrupt the disease process."
Although Alzheimer's is not an inevitable part of aging, age is certainly one of the greatest risk factors for the disease. Just 1 to 3 percent of Americans ages 65 to 74 have Alzheimer's, but 30 to 40 percent of those 85 and older are affected, and approximately half of all people over age 90 will develop the disease. Alzheimer's affects about 4 million Americans today and, unless a cure or preventive strategy can be found, 14 million will have the disease by 2050.
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