Genetic Testing for Alzheimer’s Disease

Swank Center for Memory Care and Geriatric Consultation, ChristianaCare
Graphic of a brain a DNA molecule regarding genetic testing for Alzheimer's
Learn about the most common genes associated with the early- and late-onset forms of Alzheimer’s disease, and the current recommendations for genetic testing.

Can Alzheimer’s or other forms of dementia be passed along in the genes we inherit?

This is a very common question people ask, and the answer is not the same for all kinds of dementia. In this article we will focus on Alzheimer’s disease (AD).

Genes: A Brief Background

The genes inherited from our parents and encoded in our DNA affect many aspects of our health. They guide the construction, operation, and repair of our bodies throughout life. Our parents have two “alleles” (pronounced uh-leels) or versions of each gene, and we inherit one allele for each gene site from each of our parents. This is why siblings have unique characteristics unless they are identical twins.

Specific alleles that are passed down through a family can affect the likelihood of resisting or developing many diseases. Another way in which alleles may increase the likelihood of developing a disease is the occurrence of spontaneous changes in the structure of an allele, called a mutation. A small chemical change in an allele can have profound effects on a person’s health. An altered gene may produce an altered protein that creates havoc in the body.

Genes and Alzheimer’s Disease

Most Cases of Alzheimer’s are Not Caused by a Single Gene

The good news is that most cases of Alzheimer’s disease (AD) are not passed along by a single gene. Among the millions of people in the world affected by AD, those known to have developed the disease due to the inheritance of a single gene account for a very small percentage.

The bad news is that even without inheriting one of the genes that are known to transmit AD, the disease is still a significant health risk for any older adult.

Early-Onset Alzheimer’s

About one in twenty people with AD have the early-onset form of the disease (EOAD), defined as beginning before age 60. In only a minority of cases is EOAD attributable to the inheritance of at least one gene allele that is linked with the disease.

At three specific gene locations, we know of mutated or duplicated alleles that make the development of AD likely, whether the allele is abnormal through inheritance or mutation. The harmful allele linked with the first of these genes, the gene for amyloid precursor protein (APP), increases APP’s affinity for an enzyme that promotes the creation of a toxic protein, called beta amyloid.  The other two important alleles linked with EOAD also increase the production of beta amyloid. They are called presenilin 1 (PSEN1) and presenilin 2 (PSEN2).

Late-Onset Alzheimer’s

The inheritance of late-onset Alzheimer’s disease (LOAD), which is a far more common type of AD, has not been linked with any single gene. The risk of developing LOAD, however, is affected by various genetic profiles.

The most studied genetic risk factor for LOAD is the apolipoprotein E (APOE) gene, which can occur in any combination of three possible alleles: ε2, ε3, and ε4. Each of your parents contributed one of these alleles to your genome.

If you have one ε4 allele, your risk for developing LOAD is increased by a factor of 2 or 3. If you have two of the ε4 alleles, your risk increased by a factor of 8. On the other hand, the ε2 allele may be protective.

Because the risk for LOAD is affected by multiple genetic and environmental factors, inheritance is not clear-cut.

Alzheimer’s Genetic Testing: Understanding the Pros and Cons

Early-Onset Alzheimer’s

A person with EOAD and a family history that includes 3 or more generations of EOAD genetic relatives is a good candidate for testing of PSEN1, PSEN2, and APP and is more likely than not to show a positive result. That information can be useful in confirming an EOAD diagnosis or in providing genetic counseling about the risk of passing along AD to the next generation. A positive test becomes less likely with a later age of onset and/or a smaller number of affected relatives.

Late-Onset Alzheimer’s

With LOAD, the additional question of whether to test for the APOE allele is raised. Carrying one or two ε4 alleles is an AD risk factor and also can increase the damaging effect of various environmental factors such as smoking or head injury. Yet up to 75 percent of people with one ε4 allele remain free of the disease and up to half of people with AD do not carry the ε4 allele at all.

A positive or negative APOE test could, therefore, provide confusing or even misleading information to an individual interested in assessing his or her risk of developing or passing along AD. APOE testing, therefore, is not generally recommended.


What do we make of this? Presently, genetic testing’s role is limited. If the goal of testing is the assessment of risk, there are other less costly, more practical approaches to risk assessment.

While scientists are working to develop blood tests for assessing risk, what we can do immediately, however, is to monitor measures of health such as blood pressure, sleep quality, exercise frequency, glucose metabolism, and lipid profile. These will provide useful information regarding dementia risk. More importantly, these measures will point toward lifestyle changes that are risk-reducing!


Further reading: 

Farrer LA, Brin MF, Elsas L, et al. American College of Medical Genetics/American Society of Human Genetics Working Group on APOE and Alzheimer’s Disease: statement on use of apolipoprotein E testing for Alzheimer’s disease. JAMA 1995;274:1627-9.

Lleo A, Blesa R, Queralt R, et al. Frequency of mutations in the presenilin and amyloid precursor protein genes in early-onset Alzheimer disease in Spain. Arch Neurol 2002:59:1759-63.

Loy CT, Schofield PR, Turner AM, et al. Genetics of dementia. Lancet 2014;383: 828-40.

Pihlstrom L, Wiethoff S, Houlden H. Chapter 22. Genetics of neurodegenerative diseases: an overview. Handbook of Clinical Neurology. Vol 145. 2018.

Verheijen J, Sleegers K. Understanding Alzheimer Disease at the interface between genetics and transcriptomics. Trends in Genetics 2018,


This content was first posted on: November 11, 2019

The information provided here is a public service of the BrightFocus Foundation and should not in any way substitute for personalized advice of a qualified healthcare professional; it is not intended to constitute medical advice. Please consult your physician for personalized medical advice. BrightFocus Foundation does not endorse any medical product, therapy, or resources mentioned or listed in this article. All medications and supplements should only be taken under medical supervision. Also, although we make every effort to keep the medical information on our website updated, we cannot guarantee that the posted information reflects the most up-to-date research.

These articles do not imply an endorsement of BrightFocus by the author or their institution, nor do they imply an endorsement of the institution or author by BrightFocus.

Some of the content may be adapted from other sources, which will be clearly identified within the article.

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