Family history is not necessary for an individual to develop Alzheimer’s. However, research shows that those who have a parent or sibling with Alzheimer's are more likely to develop the disease than those who do not have a first-degree relative with Alzheimer’s. Those who have more than one first-degree relative with Alzheimer’s are at an even higher risk. When diseases like Alzheimer's and other dementias tend to run in families, either genetics (hereditary factors), environmental factors — or both — may play a role.
Genetics and Alzheimer’s
There are two categories of genes that influence whether a person develops a disease: (1) risk genes and (2) deterministic genes. Researchers have identified hereditary Alzheimer's genes in both categories.
- Risk genes increase the likelihood of developing a disease but do not guarantee it will happen. Researchers have found several genes that increase the risk of Alzheimer's. APOE-e4 is the first risk gene identified and remains the gene with strongest impact on risk. Researchers estimate that between 40-65% of people diagnosed with Alzheimer's have the APOE-e4 gene.
APOE-e4 is one of three common forms of the APOE gene; the others are APOE-e2 and APOE-e3. We all inherit a copy of some form of APOE from each parent. Those who inherit one copy of APOE-e4 from their mother or father have an increased risk of developing Alzheimer's. Those who inherit two copies from their mother and father have an even higher risk, but not a certainty. In addition to raising risk, APOE-e4 may tend to make symptoms appear at a younger age than usual.
An estimated 20-30% of individuals in the United States have one or two copies of APOE-e4; approximately 2% of the U.S. population has two copies of APOE-e4.
Genetic tests are available for both APOE-e4 and the rare genes that directly cause Alzheimer’s. However, health care professionals do not currently recommend routine genetic testing for Alzheimer’s disease. Testing for APOE-e4 is sometimes included as a part of research studies.
- Deterministic genes directly cause a disease, guaranteeing that anyone who inherits one will develop a disorder. Scientists have found rare genes that cause Alzheimer's in only a few hundred extended families worldwide. These genes, which are estimated to account for 1% or less of Alzheimer's cases, cause familial early-onset forms in which symptoms usually develop between a person's early 40s and mid-50s. The vast majority of individuals with Alzheimer's have late-onset disease, occurring at age 65 or later.
Although the hereditary genes that cause "familial Alzheimer's" are rare, their discovery has provided important clues that help our understanding of Alzheimer's. All of these genes affect processing or production of beta-amyloid, the protein fragment that is the main component of plaques. Beta-amyloid is a prime suspect in decline and death of brain cells. Aducanumab (Aduhelm™), a drug granted accelerated approval by the FDA, is the first therapy to demonstrate that removing amyloid from the brain is reasonably likely to reduce cognitive and functional decline in people living with early Alzheimer’s. Several other amyloid-targeting therapies are also in development.
Two international investigations are under way to gain further insight into Alzheimer's disease by studying individuals with deterministic Alzheimer's genes: (1) The Dominantly Inherited Alzheimer Network (DIAN), funded by the National Institute on Aging (NIA), includes 10 flagship research centers in the United States, the United Kingdom and Australia. (2) The Alzheimer's Prevention Initiative (API) focuses on an extended family in Antioquia, Colombia in South America. At 5,000 members, this is the world's largest family in which a gene that causes Alzheimer's has been identified. API collaborators include DIAN.
Genetic tests are available for both APOE-e4 and the rare genes that directly cause Alzheimer's. The Alzheimer’s Association cautions against routine genetic testing for Alzheimer’s disease risk until an individual has received proper counseling and understands the information necessary to make an informed decision, including the social and economic factors that could be impacted by having this genetic information. However, there may be specific instances when an individual living with Alzheimer’s should discuss genetic testing with their physician, as the results could impact a treatment decision. For example, people who are eligible to take anti-amyloid treatments such as aducanumab may be at an increased risk for a serious side effect if they carry the APOE-e4 gene. Individuals should seek the services of a genetic counselor before and after deciding to undergo testing.
About at-home genetic tests
The Alzheimer’s Association suggests that you talk to a genetic counselor before deciding to take an at-home test and, if you decide to get genetic testing for Alzheimer’s, again after you receive the results. The National Society of Genetic Counselors website provides a searchable directory to locate a counselor. With an unsupervised, at-home test, there is a real possibility of misunderstanding results, which could result in making misinformed decisions about your health. If you are already experiencing symptoms of cognitive decline, see a health care professional for a full evaluation.
23 Chromosome Pairs; 4 Alzheimer's Genes Identified:
Amyloid precursor protein (APP),
discovered in 1987, is the first gene with mutations found to cause an inherited form of Alzheimer's.
identified in 1992, is the second gene with mutations found to cause inherited Alzheimer's. Variations in this gene are the most common cause of inherited Alzheimer's.
discovered 1993, is the third gene with mutations found to cause inherited Alzheimer's.
Apolipoprotein E-e4 (APOE4),
discovered in 1993, is the first gene variation found to increase risk of Alzheimer's and remains the risk gene with the greatest known impact. Having this mutation, however, does not mean that a person will develop the disease.
A closer look at genes linked to Alzheimer’s
The 23 human chromosome pairs contain all of the 30,000 genes that code the biological blueprint for a human being. This interactive illustration highlights the chromosomes containing each of the three genes that cause familial Alzheimer's and the gene with the greatest impact on Alzheimer's risk.