Genes and dementia: APOE and family risk

Many people who watched a parent live with dementia wonder, "Will this happen to me?" Genes are part of the answer, but usually a smaller part than people fear. For most families, genes raise or lower the odds. They do not decide the future.¹

This page explains the main dementia genes in plain words. It covers the common APOE gene, the rare genes that run strongly in families, what a test can and cannot tell you, and how the law protects your genetic information.

Two kinds of dementia genes

Genes are instructions inside every cell, passed down from both parents. When it comes to dementia, they fall into two groups.¹

Sources for this comparison: Alzheimer's Association, MedlinePlus Genetics and AFTD.^1,2,7

Researchers also suspect more than 100 other genes each nudge Alzheimer's risk by a small amount.¹ Age is still the biggest risk of all. Heart health, hearing, activity and other daily factors matter too. See ways to lower your risk.

The APOE gene

Everyone has the APOE gene. It helps carry fats like cholesterol in the body. You get one copy from each parent, and each copy comes in one of three main forms: e2, e3 or e4.²

• e3 is the most common form. More than half of people carry it.²
• e4 raises the risk of late-onset Alzheimer's. One copy raises it, and two copies raise it more.^1,2 It may also go along with memory loss starting at a younger age.²
• e2 is the third main form.²

How common is APOE e4?

About 20% to 30% of people in the U.S. have one or two copies of e4. About 2 in 100 people have two copies.¹ Among people diagnosed with Alzheimer's, roughly 40% to 65% carry e4.¹

That means two things. Many people with e4 never get Alzheimer's. And about a third or more of people with Alzheimer's do not have e4 at all.^1,2 The effect of e4 also differs between groups of people around the world.¹

Two copies of e4 (e4 homozygotes)

A person with two copies of e4 is called an e4 homozygote. A large 2024 study in Nature Medicine looked closely at this group. Almost all had Alzheimer's changes in their spinal fluid by age 65. About 3 in 4 had amyloid (a sticky protein that builds up between brain cells) on PET scans by that age. On average, their symptoms began around age 65, earlier than in people with other APOE types.⁴

The study authors argued that having two copies should be seen as a genetic form of Alzheimer's, not just a risk factor.⁴ This is an important finding for research. But it still does not tell any one person exactly when, or whether, symptoms will begin. A doctor or genetic counselor can help put it in context.

APOE and the new Alzheimer's drugs

Two drugs, lecanemab (Leqembi) and donanemab (Kisunla), remove amyloid from the brain. Both can cause ARIA (amyloid-related imaging abnormalities): brain swelling or small bleeds that show up on MRI scans. See ARIA: brain swelling and bleeding.

Both FDA labels carry a boxed warning, the FDA's strongest kind. They say people with two copies of e4 have more ARIA, including more serious ARIA, than others. Both labels say doctors should test for APOE e4 before starting, after talking through what the result could mean.^5,6

Source for the table: FDA prescribing information for each drug.^5,6 The donanemab numbers come from the original trial dosing plan. The label now recommends a different starting schedule.⁶

For lecanemab, ARIA swelling that caused symptoms happened in about 9 in 100 people with two copies of e4. That compares with about 2 in 100 with one copy, and 1 in 100 with none.⁵

A person can still choose to be treated without an APOE test. But then no one can tell whether they are in the higher-risk group.^5,6 An APOE result for this purpose can also tell family members something about their own genes. That is one more reason to talk it through first.¹ See are anti-amyloid treatments right for us?

Rare genes that run in families

Early-onset Alzheimer's: APP, PSEN1 and PSEN2

Changes (variants) in three genes, APP, PSEN1 and PSEN2, can cause familial early-onset Alzheimer's. Symptoms usually begin between the early 40s and mid-50s, though sometimes earlier or later.^1,2 These families are rare. Together they make up 1% or less of all people with Alzheimer's.¹

These genes pass down in a pattern called autosomal dominant. Only one changed copy is needed to cause the disease.² A parent with the gene has a 50% chance (1 in 2) of passing it to each child.³

A related point: people with Down syndrome have three copies of the APP gene instead of two. They have a higher risk of Alzheimer's.² See Down syndrome and Alzheimer's.

Frontotemporal dementia: MAPT, GRN and C9orf72

Frontotemporal dementia (FTD) often starts younger than Alzheimer's. It changes behavior, personality or language. About 4 in 10 people with FTD have a family history of FTD or a related illness. About 1 in 5 has a clear genetic cause.⁷

More than a dozen genes can cause FTD. The three most common are C9orf72, GRN and MAPT. The C9orf72 gene can also cause ALS (amyotrophic lateral sclerosis, a disease that weakens muscles), sometimes in the same family.⁷

The Association for Frontotemporal Degeneration (AFTD) suggests that anyone diagnosed with FTD be offered genetic counseling and the choice to test, even without a family history.⁷ Its HelpLine is 1-866-507-7222.⁷

Huntington's disease is another inherited illness that affects thinking, movement and mood. It has its own page.

Signs your family may carry one of these genes

These are clues to share with a doctor or genetic counselor:^1,7,8

• Several relatives in more than one generation had dementia, ALS or a similar illness
• Dementia started before age 65, especially in the 40s or 50s
• A relative already tested positive for a causing gene

Should you get tested?

For most people, an APOE test does not help much. It cannot say whether you will get Alzheimer's. Expert guidelines from genetics groups advise against routine APOE testing for people without symptoms in families where a strong inherited form is unlikely.⁸ There is also no medicine yet proven to prevent Alzheimer's in e4 carriers.

Testing may make more sense when:^5,6,8,11

• You are about to start lecanemab or donanemab
• A person has early-onset dementia and a family history of dementia, or an unknown family history
• A family has a known causing gene, or a pattern that suggests one
• You want to join a research study for people with a family gene

When a family gene is suspected, it is best to test a relative who already has symptoms first, if possible. A positive result then makes testing others in the family more useful.⁸

Questions to ask yourself first

How would I feel if the result is bad news?

Some people feel relief from knowing. Others feel worry or sadness for a long time. A counselor can help you think this through ahead of time. If worry starts to take over, see our pages on anxiety and depression.

What would I do differently?

Some people use results to plan finances, make legal papers early, join a study or change health habits. If nothing would change, you may decide not to test. See planning ahead.

Who else does this affect?

Your genes are shared with your parents, brothers, sisters and children. Your result can reveal their risk too, even if they did not want to know.¹

Should I buy insurance before testing?

GINA does not cover long-term care, life or disability insurance.⁹ Some people choose to apply for those before they test. Learn more about long-term care insurance.

Why genetic counseling comes first

A genetic counselor is a health professional trained in genetics and in helping people make hard choices. The Alzheimer's Association advises counseling both before a test is ordered and when results come back.¹

Expert guidelines describe what good counseling includes:⁸

• A family health history going back three generations
• A talk about every possible result, including an unclear one
• Thinking about how results could affect your feelings, insurance and family
• Choosing a support person to be with you when you get results
• For people with symptoms, a family member or legal decision-maker present

The same guidelines say children should not be tested for adult-onset Alzheimer's genes.⁸

You can find a genetic counselor through the National Society of Genetic Counselors at nsgc.org.¹ Counseling can happen in person or by video.⁸ Ask about cost before testing, since coverage depends on your plan and why the test is ordered.

Home DNA tests

Some home DNA kits report APOE e4, and some home tests do not need a doctor's order.¹ The FDA warns that no test is 100% accurate. A positive result does not mean you will get the disease. A negative result does not mean you won't.¹⁰ The genetics guidelines advise against home APOE testing.⁸

If a home test surprises you, do not panic. Talk with your doctor or a genetic counselor before making any health decisions. A doctor may order a confirming test.¹⁰

What the law protects: GINA

The Genetic Information Nondiscrimination Act (GINA) is a 2008 federal law. It has two main parts.⁹

Source for the table: National Human Genome Research Institute.⁹

GINA sets a floor. Some states add more protection, including for life, disability or long-term care insurance.⁹ Laws differ from state to state, so check yours before testing if this matters to you.

Research for families with a dementia gene

The Dominantly Inherited Alzheimer Network (DIAN) studies families with inherited early-onset Alzheimer's. It runs a registry and drug trials for people who have or are at risk for this form.¹¹ Other studies welcome people with APOE e4. See joining a dementia clinical trial.

When to get help

• Talk with your doctor if dementia runs in your family and you have new memory or behavior changes. See the first doctor visit.
• Ask for a genetic counselor if a relative had dementia before 65 or tested positive for a dementia gene.
• If test results leave you feeling hopeless or thinking about suicide, call or text 988 to reach the 988 Suicide & Crisis Lifeline any time. If you are in danger right now, call 911.

Genes are one piece of the picture. Back to getting a dementia diagnosis.

Education only. This page is general information written from the sources listed. It is not medical, legal or financial advice and does not replace a doctor, therapist or lawyer who knows your situation. How we write and check pages.