Having a family member with Alzheimer’s increases the risk of developing the disease. However, only a handful of people with Alzheimer’s-fewer than 2 to 3 percent-have the disease as a result of one of three identifiable defective genes, or gene mutations. A person carrying one of these three mutations will inevitably develop Alzheimer’s if he or she lives long enough.
In families with one of these mutations, Alzheimer’s disease is carried as a dominant trait; each offspring has a 50 percent chance of inheriting the abnormal gene, on one of three chromosomes-the amyloid precursor protein (APP) gene on chromosome 21, the presenilin-1 (PS-1) gene on chromosome 14, and the presenilin-2 (PS-2) gene on chromosome 1. Those with an altered APP gene usually develop the disease between the ages of 40 and 65. Those who carry a PS-1 mutation may show signs of Alzheimer’s as early as age 30, whereas people with PS-2 defects develop the disease between ages 40 and 90. Across the population, the prevalence of these gene mutations is low.
While scientists have identified hundreds of different genetic variants (a single gene can have many variants) that are involved in Alzheimer’s disease, the total proportion of Alzheimer’s disease accounted for by these different mutations is extremely small.
To date, researchers have also found more than 20 genetic variations linked to Alzheimer’s disease that are not abnormalities or mutations, but normal variations in genes that we all carry. Called polymorphisms, these genes differ between people in the same way that genes code for differences in hair or eye color. Some of these variations have been linked to increased risks of Alzheimer’s disease. Each of these genes is likely to contribute only a little bit (probably less than 1 percent) to the overall incidence of the disease. However, the polymorphism associated with apolipoprotein E (APOE) is the most important and appears to exert relatively strong effects.
Also important to know: Having a genetic predisposition to Alzheimer’s disease is not the same thing as carrying a genetic mutation. A predisposition means that, although the disease “runs in the family,” it is not associated with one of the genetic defects discussed above. Some family members develop the disease, while others don’t.
A predisposition suggests that other risk factors interact with a person’s genetic makeup to increase the likelihood that Alzheimer’s will develop, or cause the disease to begin earlier in life. In one study of identical twins, who share an identical genetic makeup, the age of Alzheimer’s onset varied by as much as 15 years. By studying people from different ethnic, racial, and social groups, scientists may discover the full range of additional risk factors. These findings, in turn, could provide new insights into a single or multiple triggers for Alzheimer’s disease.