Genetic testing for Alzheimer’s disease (AD) is available for individuals concerned about their risk or family history. AD is the most frequent cause of dementia, accounting for 60% to 80% of all cases, and its development involves a complex interplay of genetic, environmental, and lifestyle factors. While testing provides valuable insights into an individual’s predisposition, it requires careful consideration of the genes tested, the accuracy of the results, and the need for professional guidance. Understanding the options and implications is paramount before proceeding.
Understanding the Genes Involved in Alzheimer’s
Genetic risk for Alzheimer’s disease is categorized by two distinct groups of genes: risk factors for the common late-onset form and deterministic mutations for the rare early-onset form. The most significant genetic risk factor is the Apolipoprotein E gene, or APOE. This gene has three common variants, or alleles, with the APOE e4 allele being strongly associated with increased risk for late-onset AD, which typically begins after age 65.
Inheriting the APOE e4 allele raises the likelihood of developing the disease but does not guarantee it will occur. In contrast, the much rarer Early-Onset Familial AD (EOAD), which strikes individuals before age 65, is linked to deterministic genes: APP (Amyloid Precursor Protein), PSEN1 (Presenilin 1), and PSEN2 (Presenilin 2).
A mutation in one of these three genes virtually guarantees the development of AD, with PSEN1 and APP mutations having nearly complete penetrance. These mutations follow an autosomal dominant inheritance pattern, meaning a child has a 50% chance of inheriting the altered gene. Testing for these deterministic genes is typically recommended only when a person shows symptoms or has a strong family history of EOAD.
Clinical Testing Versus Direct-to-Consumer Options
Individuals interested in genetic testing have two main avenues: clinical testing or direct-to-consumer (DTC) testing. Clinical testing is ordered by a healthcare professional, such as a neurologist or genetic counselor, often due to a medical indication like a strong family history of early-onset disease. This pathway ensures the test is performed by a certified laboratory and includes appropriate pre- and post-test counseling.
DTC testing, offered by companies like 23andMe, allows individuals to purchase a test kit without a doctor’s order. These tests usually screen only for the APOE gene and its e4 risk allele, assessing risk for late-onset AD. They do not typically test for deterministic genes like PSEN1 and PSEN2. While convenient, DTC testing often lacks professional oversight, requiring the consumer to interpret complex risk information independently.
Interpreting Genetic Test Results
Interpreting Alzheimer’s genetic test results requires understanding the difference between a risk factor and a certain diagnosis. An APOE gene test determines how many copies of the e4 allele an individual has (zero, one, or two). The presence of one copy of e4 approximately doubles or triples the lifetime risk of developing late-onset AD compared to the general population.
Having two copies of the e4 allele, the highest-risk genotype, increases the risk 8 to 12 times. However, the APOE result is not a diagnosis; many people with the e4 allele never develop AD, and many without it do develop the condition. The result indicates a change in probability, with lifestyle and other factors playing a significant part.
For deterministic genes (APP, PSEN1, PSEN2), a positive result is highly predictive, indicating a near-certainty of developing the disease if the individual lives to the typical age of onset. A negative result for these specific genes does not eliminate all risk, as the individual still faces the general population risk for the common form of AD.
Legal Protections for Genetic Information
Federal laws, including the Health Insurance Portability and Accountability Act (HIPAA) and the Genetic Information Nondiscrimination Act (GINA), prohibit health insurers and employers from using genetic information to deny coverage or make employment decisions. GINA does not extend these protections to life insurance, disability insurance, or long-term care insurance.
The Essential Role of Genetic Counseling
Genetic counseling is an essential part of the testing process. A genetic counselor is a healthcare professional who specializes in explaining the complexities of hereditary conditions and genetic testing. Before testing, pre-test counseling helps individuals fully understand the test’s limitations and the potential emotional impact of a positive result.
This counseling ensures informed consent and helps the person consider how results might affect family planning, career, and financial decisions. After the test, post-test counseling interprets the complex probabilities, such as the difference between a high-risk APOE genotype and a deterministic gene mutation. The counselor also offers emotional support and guides individuals toward next steps, including research trials or proactive lifestyle changes.