A very small percentage of people who develop Alzheimer's disease have the early-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 65. The genes involved are:
- Amyloid precursor protein (APP)
- Presenilin 1 (PSEN1)
- Presenilin 2 (PSEN2)
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 protein malfunctions and stick together to form neurofibrillargy 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.
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.
In the case of APOE, just because you have the e4 variety doesn't mean you'll get Alzheimer's. Although many people with APOE e4 develop Alzheimer's, many don't. Conversely, some people with no APOE e4 genes develop Alzheimer's.
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.
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.
Researchers and genes
Researchers suspect that many more genes that haven't been identified yet affect the risk of Alzheimer's disease. Such information may prove vital in the development of new ways to treat, or even prevent, Alzheimer's disease in the future.
The Alzheimer's Disease Genetics Study, sponsored by the National Institute on Aging, is examining genetic information from families that have at least two family members who have developed Alzheimer's after age 65. If your family is interested in participating in this study, visit the website for the National Cell Repository for Alzheimer's Disease.
A number of other studies are evaluating the genetics of people with Alzheimer's disease and their family members. To learn more about these studies, and whether or not they're recruiting volunteers, visit the National Institute on Aging's Alzheimer's Disease Education and Referral Center website, or ask your doctor what trials might be available.
Jan. 26, 2016
- Karch CM, et al. Alzheimer's disease genetics: From the bench to the clinic. Neuron. 2014;83:11.
- Sherva R, et al. Genetics of Alzheimer disease. http://www.uptodate.com/home. Accessed Nov. 18, 2015.
- The genetics of Alzheimer's disease. National Cell Repository for Alzheimer's Disease. https://ncrad.iu.edu/genetics_ad.html. Accessed Nov. 19, 2015.
- Alzheimer's disease genetics fact sheet. National Institute on Aging. https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-genetics-fact-sheet. Accessed Nov. 18, 2015.
- Carch CM, et al. Alzheimer's disease risk genes and mechanisms of disease pathogenesis. Biological Psychiatry. 2015;77:43.
- Risk factors. Alzheimer's Association. http://www.alz.org/alzheimers_disease_causes_risk_factors.asp. Accessed Nov. 19, 2015.
- Genetic testing topic sheet. Alzheimer's Association. http://www.alz.org/alzheimers_disease_causes_risk_factors.asp#genetics. Accessed Nov. 19, 2015.