Having at least one APOE e4 gene increases your risk of developing Alzheimer's disease two- to threefold. If you have two APOE e4 genes, your risk is even higher, approximately eight- to twelvefold. Other genetic and environmental factors likely are involved in the development of Alzheimer's disease. As research on the genetics of Alzheimer's progresses, researchers are uncovering links between late-onset Alzheimer's and a number of other genes.
Several examples include:. Researchers are continuing to learn more about the basic mechanisms of Alzheimer's disease, which may potentially lead to new ways to treat and prevent the disease.
As with APOE , these genes are risk factors, not direct causes. In other words, having a variation of one of these genes may increase your risk of Alzheimer's. However, not everyone who has one will develop Alzheimer's disease. A very small percentage of people who develop Alzheimer's disease have the young-onset type.
Signs and symptoms of this type usually appear between ages 30 and 60 years. This type of Alzheimer's disease is very strongly linked to your genes.
Scientists have identified three genes in which mutations cause early-onset Alzheimer's disease. If you inherit one of these mutated genes from either parent, you will probably have Alzheimer's symptoms before age The genes involved are:. Mutations of these genes cause the production of excessive amounts of a toxic protein fragment called amyloid-beta peptide. This peptide can build up in the brain to form clumps called amyloid plaques, which are characteristic of Alzheimer's disease.
A buildup of toxic amyloid-beta peptide and amyloid plaques may lead to the death of nerve cells and the progressive signs and symptoms of this disorder. As amyloid plaques collect in the brain, tau proteins malfunction and stick together to form neurofibrillary tangles. These tangles are associated with the abnormal brain functions seen in Alzheimer's disease. However, some people who have early-onset Alzheimer's don't have mutations in these three genes.
That suggests that some early-onset forms of Alzheimer's disease are linked to other genetic mutations or other factors that haven't been identified yet. This research network includes observational studies and clinical trials. Most experts don't recommend genetic testing for late-onset Alzheimer's.
In some instances of early-onset Alzheimer's, however, genetic testing may be appropriate. Most clinicians discourage testing for the APOE genotype because the results are difficult to interpret. And doctors can generally diagnose Alzheimer's disease without the use of genetic testing. Testing for the mutant genes that have been linked to early-onset Alzheimer's — APP , PSEN1 and PSEN2 — may provide more-certain results if you're showing early symptoms or if you have a family history of early-onset disease.
Genetic testing for early-onset Alzheimer's may also have implications for current and future therapeutic drug trials as well as for family planning.
Before being tested, it's important to weigh the emotional consequences of having that information. The results may affect your eligibility for certain forms of insurance, such as disability, long-term care and life insurance.
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Krugylak L. Thresholds and sample sizes. See More About Genetics and Genomics. Save Preferences. Privacy Policy Terms of Use. This Issue. Citations View Metrics. Twitter Facebook More LinkedIn. Original Contribution.
William S. Family Data. Generation of Marker Data. Statistical Analysis. Access your subscriptions. Access through your institution. Add or change institution. Free access to newly published articles. The APOE gene is involved in making a protein that helps carry cholesterol and other types of fat in the bloodstream.
APOE comes in several different forms, or alleles. Each person inherits two APOE alleles, one from each biological parent. Some cases are caused by an inherited change in one of three genes.
Mutations in these genes result in the production of abnormal proteins that are associated with the disease. Each of these mutations plays a role in the breakdown of APP, a protein whose precise function is not yet fully understood. Studies are ongoing to identify additional genetic risk variants.
Researchers believe this is because people with Down syndrome are born with an extra copy of chromosome 21, which carries the APP gene. A blood test can identify which APOE alleles a person has, but results cannot predict who will or will not develop Alzheimer's disease. Currently, APOE testing is used primarily in research settings to identify study participants who may have an increased risk of developing Alzheimer's.
This knowledge helps scientists look for early brain changes in participants and compare the effectiveness of possible treatments for people with different APOE profiles.
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