Genetic Testing for Alzheimer's

By Dr. Brandon Colby MD, a Personalized Preventive Medicine specialist and expert in clinical genomics.

Alzheimer's disease is the most common type of dementia, characterized by progressive cognitive decline affecting memory, orientation, language, and attention. It places a significant burden on patients, their loved ones, and caregivers. Understanding your genetic risk is one of the most powerful steps you can take toward prevention.

Is Alzheimer's Genetic?

Alzheimer's disease is not purely genetic, but genetic information plays an important role in determining risk. It is a multifactorial disease, meaning that many different factors, including lifestyle, environment, and genetics, contribute to whether a person develops it.

Certain genetic variants can increase your risk, but elevated risk does not mean the disease is inevitable. Preventive measures can offset genetic predispositions, and practically anyone can benefit from them regardless of their genetic profile.

The APOE Gene and Alzheimer's Risk

One gene plays a particularly important role: the APOE gene. It produces a protein called apolipoprotein E, which helps eliminate amyloid-beta deposits that can accumulate and form the plaques associated with Alzheimer's disease. The three alleles of this gene affect risk differently.

• APOE2 is the least common allele. It enables greater production of apolipoprotein E, offering some protection against Alzheimer's disease.
• APOE3 is the most common allele and is considered neutral, though research suggests it may increase risk slightly when combined with variants in other genes.
• APOE4 reduces the production of apolipoprotein E, increasing risk. Inheriting one copy from a parent elevates risk, and inheriting two copies increases it further.

Other genes associated with late-onset Alzheimer's risk include ABCA7, GAB2, TOMM40, CLU, CR1, PICALM, PLD3, TREM2, and SORL1.

Early-Onset Alzheimer's and Genetics

Early-onset familial Alzheimer's disease (eFAD) accounts for approximately 0.1 percent of all Alzheimer's cases. It is caused by mutations in three specific genes: Amyloid precursor protein (APP), Presenilin 1 (PSEN1), and Presenilin 2 (PSEN2). Unlike late-onset Alzheimer's, eFAD follows an autosomal dominant inheritance pattern, meaning a mutation in just one copy of the gene is sufficient to cause the disease. Because the APP gene is located on chromosome 21, people with Down syndrome carry an increased risk of early-onset Alzheimer's.

Can You Genetically Test for Alzheimer's?

No genetic test can predict with certainty whether a person will develop Alzheimer's disease. However, DNA testing can identify whether you carry variants that increase your risk. When all associated genes are considered together, genetic analysis has been estimated to predict up to 90 percent of a person's risk of developing Alzheimer's.

If results reveal elevated risk, that information can guide a prevention plan. Many preventive strategies have been shown to delay or reduce the onset and progression of Alzheimer's. You should discuss results with a neurology specialist or genetic counselor, particularly if you have other risk factors such as family history, cardiovascular disease, or a history of traumatic brain injury.

Alzheimer's DNA Test Options

Single-gene testing can identify which APOE variant you carry. Whole Genome Sequencing (WGS) goes further, sequencing every base pair in your genome. In addition to revealing mutations in genes associated with Alzheimer's, such as APOE, GAB2, TOMM40, APP, PSEN1, and PSEN2, WGS provides information on risk for other multifactorial diseases, carrier status for genetic disorders, medication response, and wellness insights.

Research has also found that individuals with early-onset Alzheimer's often carry multiple contributing mutations, which makes comprehensive testing such as WGS more informative than single-gene approaches.

Where to Get Genetic Testing for Alzheimer's

Genetic testing for Alzheimer's is available through healthcare providers, genetic counselors, and direct-to-consumer services. Government-funded testing may be available in some regions under specific circumstances, such as the NHS in the United Kingdom, but these tests are typically limited in scope and require a clinical consultation.

Sequencing offers clinical-grade Whole Genome Sequencing, reading 100% of your DNA across over 30,000 genes. This provides the most comprehensive picture of your Alzheimer's risk and overall genetic health. You can also upload raw DNA data from another provider to access Alzheimer's risk analysis apps in the Sequencing Partner Marketplace.

Note that tests analyzing only the APOE gene leave out the many other genes now known to contribute to Alzheimer's risk. Whole Genome Sequencing ensures a complete analysis.

References

1. Goldman JS, et al. Genetic counseling and testing for Alzheimer disease. Genet Med. 2011;13(6):597-605.
2. Colby MD, B. Outsmart Your Genes. 2010.
3. Alzheimer's genes: Are you at risk? Mayo Clinic. 2019.
4. Early-Onset Alzheimer's Disease. Johns Hopkins Medicine.
5. Alzheimer's Disease Genetics Fact Sheet. NIH National Institute on Aging.
6. Causes and Risk Factors for Alzheimer's Disease. Alzheimer's Association.
7. Genetic Testing and Counseling for Early Onset Familial Alzheimer Disease. ALZFORUM.
8. Cochran JN, et al. Genome sequencing for early-onset or atypical dementia. Cold Spring Harbor Mol Case Studies. 2019;5(6):a003491.

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