Alzheimer’s disease (AD) is a progressive neurological condition that destroys memory and thinking skills, eventually affecting the ability to carry out simple tasks. While most cases are “sporadic,” genetics plays a complex role in a person’s overall risk. The presence of certain gene variants can influence the likelihood of developing the disease, though testing usually reveals a probability, not a certainty. Understanding the types of genetic markers and testing options is the first step in making an informed decision.
The Key Genetic Markers
The genetic landscape of Alzheimer’s disease is divided into two categories based on age of onset. Late-onset AD, the most common form, typically begins after age 65 and is influenced by risk factor genes. The most significant genetic risk factor identified for late-onset AD is the apolipoprotein E (\(APOE\)) gene.
The \(APOE\) gene has three common variants: \(APOE2\), \(APOE3\), and \(APOE4\). The \(APOE3\) allele is the most common and is considered neutral in terms of risk. The \(APOE2\) allele offers some protection against developing the disease. Conversely, inheriting the \(APOE4\) allele increases the risk of developing late-onset AD and is associated with an earlier age of onset.
Early-onset familial AD (EOAD) is a much rarer form, accounting for less than 5% of all cases, and can start as early as a person’s 30s or 40s. This form is caused by deterministic mutations in one of three genes: Amyloid Precursor Protein (\(APP\)), Presenilin 1 (\(PSEN1\)), or Presenilin 2 (\(PSEN2\)). A single copy of a pathogenic mutation in one of these genes is sufficient to cause the disease, a pattern known as autosomal dominant inheritance. These mutations alter the processing of the amyloid-beta protein, leading to the accumulation of toxic plaques.
Types of Genetic Testing Available
Testing for Alzheimer’s related genes is available through two main avenues: clinical testing ordered by a healthcare professional or Direct-to-Consumer (DTC) testing. Clinical genetic testing is performed in a medical setting, often after consulting with a neurologist or genetic counselor. This testing is comprehensive and may include analysis for the \(APP\), \(PSEN1\), and \(PSEN2\) genes if a strong family history of early-onset AD is present.
A healthcare provider collects a sample via a blood draw or cheek swab, and results are returned directly to the ordering physician for interpretation. DTC testing is purchased directly by the consumer online, using a simple saliva sample collected at home. These tests primarily report on the \(APOE\) gene status, identifying the presence of the \(APOE4\) allele, but they do not typically screen for the rare deterministic EOAD mutations.
While DTC testing offers convenience, it often lacks the counseling and clinical context that accompanies physician-ordered testing. The FDA allows some DTC companies to offer \(APOE\) testing, but these results are not considered diagnostic and should be confirmed by a clinical laboratory if used for medical decisions. Clinical testing is often broader, encompassing a wider panel of genes that may affect dementia risk compared to the limited focus of consumer tests.
Interpreting Test Results and Risk
The meaning of a genetic test result depends entirely on which genes were analyzed. A positive result for a mutation in \(APP\), \(PSEN1\), or \(PSEN2\) is considered highly penetrant, meaning it is near-certain that the individual will develop the disease, usually at a young age. These results are typically only sought by individuals with a known history of EOAD in their family.
\(APOE\) gene results, which are the most commonly available, must be interpreted as a statistical risk factor, not a diagnosis or a guarantee. Everyone inherits two copies of the \(APOE\) gene. Inheriting one copy of the \(APOE4\) allele is associated with a two to three-fold increase in the lifetime risk of developing late-onset AD compared to those with two \(APOE3\) alleles. A person who inherits two copies of the \(APOE4\) allele faces a significantly higher risk, estimated at an eight to fifteen-fold increase.
Many people with one or two \(APOE4\) alleles never develop Alzheimer’s disease, and many people who develop the disease do not carry the \(APOE4\) allele. Therefore, an \(APOE\) test cannot predict whether a person will definitely get AD or when it might begin. Non-genetic factors like lifestyle and environment also play a role, meaning the test only provides an estimate of genetic susceptibility.
Making the Decision to Test
The choice to undergo genetic testing for Alzheimer’s risk is deeply personal and involves complex considerations. Since there is currently no cure for AD, receiving a result indicating increased risk can have a profound emotional and psychological impact. Many individuals work with a certified genetic counselor both before and after testing to prepare for possible outcomes and fully understand the implications.
Counseling helps a person explore their motivations for testing, often including a desire for “actionability”—the ability to make lifestyle changes or participate in clinical trials. For those with heightened genetic risk, engaging in health-promoting behaviors like regular exercise, a healthy diet, and cognitive stimulation offers a sense of proactive control. A positive result may also inform long-term planning regarding finances, career, and family decisions.
It is important to consider the potential for genetic discrimination, particularly concerning insurance. The federal Genetic Information Nondiscrimination Act (GINA) protects against discrimination by health insurers and employers based on genetic information. However, GINA does not extend protections to life insurance, disability insurance, or long-term care insurance. An individual who tests positive for a high-risk allele may legally face higher premiums or denial of coverage for these specific insurance products if they apply after receiving their results.