Information about Hereditary Risk Factors for Alzheimer's

Having a family member with Alzheimer's increases the risk of developing the disease. However, only a handful of Alzheimer's patients—fewer than 5%—have the disease as a result of an identifiable defective gene (a gene mutation). In families with a mutation, Alzheimer's is carried as a dominant trait (which means that 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.

The prevalence of these gene mutations is low. As an example, the defective APP gene has been found in only 25 families worldwide. Although these mutations affect only a small number of families, a person carrying one of them will inevitably develop Alzheimer's if he or she lives long enough. Those with an altered APP gene usually develop the disease between ages 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.

Researchers expect to find other genetic abnormalities linked to Alzheimer's disease. In fact, scientists have already pinpointed an area on chromosome 10 that appears to contain genes that influence the disease. A possible new gene, sortilin-related receptor L (SORL1), also has been identified. Scientists believe there may be as many as a dozen genes that contribute to Alzheimer's risk, but each is likely to contribute only a little bit to the overall incidence of the disease.

Having a genetic predisposition to Alzheimer's disease is different from 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 do not.

A predisposition suggests that other risk factors interact with a person's genetic makeup to increase the chance that he or she will develop Alzheimer's or to 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 what triggers Alzheimer's disease.

Publication Review By: Peter V. Rabins, M.D., M.P.H.

Published: 09 Mar 2011

Last Modified: 28 Aug 2015