Genetic testing for Alzheimer’s disease is available, providing results that range from a strong indication of future disease to a statistical increase in lifetime risk. Alzheimer’s is a progressive neurological disorder causing brain cells to die, leading to memory loss and cognitive decline. While most cases are late-onset and sporadic, genetics play a significant role in determining an individual’s susceptibility. Understanding the specific genes involved and the information a test provides is necessary for anyone considering genetic testing.
The Genes Linked to Alzheimer’s Risk
The genetic factors for Alzheimer’s disease fall into two distinct categories: risk genes and deterministic genes. The most well-known risk gene is Apolipoprotein E, or APOE, which is the strongest genetic risk factor for the common late-onset form of Alzheimer’s. The APOE gene has three variants, or alleles: e2, e3, and e4, with everyone inheriting one copy from each parent. The e3 allele is the most common and is considered neutral regarding risk, while the e2 allele appears to offer some protection against the disease.
The e4 allele, however, is associated with an increased likelihood of developing Alzheimer’s, and its presence can also decrease the age of disease onset. APOE is involved in lipid metabolism and cholesterol transport within the brain, and the e4 variant is thought to interfere with the clearance of amyloid-beta, a protein fragment that aggregates to form plaques characteristic of the disease.
The second category comprises deterministic genes linked to rare, early-onset familial Alzheimer’s disease (FAD), which typically begins before age 65. These genes are APP (Amyloid Precursor Protein), PSEN1 (Presenilin 1), and PSEN2 (Presenilin 2). Mutations in these genes directly cause the disease by altering the processing of the Amyloid Precursor Protein, leading to the overproduction of the amyloid-beta peptide. Inheriting a mutation in PSEN1, PSEN2, or APP means the person will almost certainly develop FAD, often in their 30s, 40s, or 50s.
Types of Genetic Testing Available
Genetic information related to Alzheimer’s disease can be obtained through two primary channels: clinical testing and direct-to-consumer (DTC) testing. Clinical testing is typically ordered by a physician, often when a patient exhibits early symptoms or has a clear family history of early-onset FAD. This comprehensive and strictly regulated process utilizes accredited laboratories to analyze a blood sample for mutations in the deterministic genes (APP, PSEN1, PSEN2) or the risk gene (APOE).
Testing for the rare deterministic genes is usually offered as diagnostic testing for symptomatic individuals or as predictive testing for asymptomatic individuals with a known FAD family history. DTC testing, conversely, is purchased directly by the consumer, usually involving a saliva sample sent to a commercial lab without a doctor’s order. Many popular DTC kits offer to test for the APOE status, specifically the e4 allele, as a susceptibility test to determine a person’s risk for late-onset Alzheimer’s.
DTC tests generally do not include full sequencing for the deterministic FAD genes, focusing instead on the common APOE risk factor. While convenient, DTC results lack the clinical oversight and professional interpretation that accompany physician-ordered testing. The limited scope means a negative result for APOE e4 does not rule out all genetic risk factors.
Interpreting Test Results and Risk
The interpretation of genetic test results depends heavily on which genes were tested and whether the individual is symptomatic. A positive result for a mutation in one of the deterministic FAD genes (APP, PSEN1, or PSEN2) carries a near-certainty, or high penetrance, that the individual will develop the disease. Because of the autosomal dominant nature of these mutations, a person has a 50% chance of passing the gene to each child.
Testing for the APOE gene, however, is purely a risk assessment for late-onset Alzheimer’s, not a diagnosis or certainty of the disease. The risk is dose-dependent, meaning it correlates with the number of e4 alleles inherited. Having one copy of APOE e4 (heterozygous) can increase the risk of developing Alzheimer’s by approximately three-fold compared to the common e3/e3 genotype.
A person who inherits two copies of the APOE e4 allele (homozygous) faces the highest genetic risk, which can be 10 to 15 times the normal risk. Despite this significant increase, even those with two e4 copies are not guaranteed to develop the disease, and many people without the e4 allele still develop Alzheimer’s. This highlights that lifestyle, environmental factors, and other genetic variants still play a substantial role in the final outcome.
Clinical Guidance and Counseling
Due to the complex nature of the results, genetic counseling is often recommended before and after any genetic testing for Alzheimer’s disease. Genetic counselors help individuals explore their motivations for testing, assess their family history, and understand the difference between risk susceptibility and a definitive diagnosis. They also discuss the potential for negative emotional impacts, such as anxiety or depression, regardless of the result.
For asymptomatic individuals, testing is generally not recommended unless there is a strong, multi-generational family history of early-onset disease, which would suggest a deterministic mutation. The counseling process also includes practical discussions about the potential for discrimination, particularly concerning long-term care and life insurance. The Genetic Information Nondiscrimination Act (GINA) provides protection against discrimination by health insurers and employers, but it does not extend to life insurance, disability insurance, or long-term care insurance.
An informed decision requires understanding that a positive result may affect personal and family planning, but it currently does not change treatment options for prevention. Counseling ensures that individuals understand that a negative test result for a known family mutation is informative, while a negative APOE result only means the risk is lower than average, not zero. Professional guidance is designed to ensure the individual is prepared for all possible outcomes.