FACT SHEET

Scientists don’t yet fully 

understand what causes 

Alzheimer’s disease. However, the more they learn about 

this devastating disease, the more 

they realize that genes* play an 

important role in its development. 

Research conducted and funded 

by the National Institute on Aging 

(NIA) at the National Institutes 

of Health and others is advancing 

the field of Alzheimer’s disease 

genetics.

The Genetics of Disease

Some diseases are caused by a 

genetic mutation, or permanent 

change in one or more specific 

genes. If a person inherits from 

a parent a genetic mutation that 

causes a certain disease, then he 

or she will usually get the disease. 

Sickle cell anemia, cystic fibrosis, 

and early-onset familial Alzheimer’s 

disease are examples of inherited 

genetic disorders.

Alzheimer’s Disease Genetics 

Alzheimer’s Disease Education & Referral (ADEAR) Center

A Service of the National Institute on Aging

National Institutes of Health

U.S. Department of Health and Human Services

*Terms in bold are defined at the end of this fact sheet.

In other diseases, a genetic variant 

may occur. This change in a gene can 

sometimes cause a disease directly. 

More often, it acts to increase or 

decrease a person’s risk of developing a disease or condition. When a 

genetic variant increases disease risk 

but does not directly cause a disease, 

it is called a genetic risk factor.

Alzheimer’s Disease Genetics

Alzheimer’s disease is an irreversible,

progressive brain disease. It is characterized by the development of amyloid 

plaques and neurofibrillary tangles, 

the loss of connections between nerve 

cells, or neurons, in the brain, and 

the death of these nerve cells. There 

are two types of Alzheimer’s—earlyonset and late-onset. Both types have 

a genetic component.

Early-Onset Alzheimer’s Disease

Early-onset Alzheimer’s disease 

occurs in people age 30 to 60. It is 

rare, representing less than 5 percent
DNA, Chromosomes, and Genes

The nucleus of almost every 

human cell contains a “blueprint” 

that carries the instructions a 

cell needs to do its job. The 

blueprint is made up of DNA 

(deoxyribonucleic acid), which is 

present in long strands that would 

stretch to nearly 6 feet in length 

if attached end to end. The DNA 

is packed tightly together with 

proteins into compact structures 

called chromosomes. Normally, 

each cell has 46 chromosomes in 23 pairs, which are inherited equally from a father 

and a mother. The DNA in nearly all cells of an individual is identical. 

Each chromosome contains many thousands of segments, called genes. People 

inherit two copies of each gene from their parents, except for genes on the X and 

Y chromosomes, which, among other functions, determine a person’s sex. The 

genes “instruct” the cell to make unique proteins that, in turn, dictate the types 

of cells made. Genes also direct almost every aspect of the cell’s construction, 

operation, and repair. Even slight changes in a gene can produce a protein that 

functions abnormally, which may lead to disease. Other changes in genes may 

increase or decrease a person’s risk of developing a particular disease.

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of all people who have Alzheimer’s. 

Some cases of early-onset Alzheimer’s 

have no known cause, but most cases 

are inherited, a type known as familial 

Alzheimer’s disease (FAD).

Familial Alzheimer’s disease is 

caused by any one of a number of 

different single-gene mutations 

on chromosomes 21, 14, and 1. 

Each of these mutations causes 

abnormal proteins to be formed. 

Mutations on chromosome 21 cause 

the formation of abnormal amyloid 

precursor protein (APP). A mutation 

on chromosome 14 causes abnormal 

presenilin 1 to be made, and a 

mutation on chromosome 1 leads 

to abnormal presenilin 2.

Scientists know that each of these 

mutations plays a role in the breakdown of APP, a protein whose precise 

function is not yet known. This 

breakdown is part of a process that 

generates harmful forms of amyloid 

Genes

23 Pairs of

Chromosomes

Cell Nucleus

Chromosome 

Pair

DNA Strand

Cell
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plaques, a hallmark of the disease. 

A child whose mother or father 

carries a genetic mutation for FAD 

has a 50/50 chance of inheriting 

that mutation. If the mutation is 

inherited, the child almost surely 

will develop FAD. 

Critical research findings about 

early-onset Alzheimer’s have helped 

identify key steps in the formation 

of brain abnormalities typical of 

Alzheimer’s disease. They have also 

led to the development of imaging 

tests that show the accumulation 

of amyloid in the living brain. In 

addition, the study of Alzheimer’s 

genetics has helped explain some 

of the variation in the age at which 

the disease develops. 

NIA-supported scientists are 

continuing this research through 

the Dominantly Inherited Alzheimer 

Network (DIAN), an international 

partnership to study families with 

a genetic mutation that causes 

early-onset Alzheimer’s disease. By 

observing the biological changes that 

occur in these families long before 

symptoms appear, scientists hope to 

gain insight into how and why the 

disease develops in both its earlyand late-onset forms. In addition, 

scientists are attempting to develop 

tests that will enable diagnosis of 

Alzheimer’s before clinical signs and 

symptoms appear, as it is likely that 

early treatment will be critical as 

therapies become available.

Late-Onset Alzheimer’s Disease

Most cases of Alzheimer’s are the 

late-onset form, which develops 

after age 60. The causes of late-onset

Alzheimer’s are not yet completely 

understood, but they likely include

a combination of genetic, environmental, and lifestyle factors that 

influence a person’s risk for developing the disease.

The single-gene mutations directly

responsible for early-onset Alzheimer’s 

disease do not seem to be involved in 

late-onset Alzheimer’s. Researchers 

have not found a specific gene that 

causes the late-onset form of the 

disease. However, one genetic risk 

factor does appear to increase a 

person’s risk of developing the disease. 

This increased risk is related to the 

apolipoprotein E (APOE) gene

found on chromosome 19. APOE 

contains the instructions for making 

a protein that helps carry cholesterol 

and other types of fat in the bloodstream. APOE comes in several 

different forms, or alleles. Three 

forms—APOE e2, APOE e3, and 

APOE e4—occur most frequently.

n APOE e2 is relatively rare and 

may provide some protection 

against the disease. If Alzheimer’s 

disease occurs in a person with 

this allele, it develops later in life 

than it would in someone with the 

APOE e4 gene. 
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n APOE e3, the most common allele, 

is believed to play a neutral role 

in the disease—neither decreasing 

nor increasing risk. 

n APOE e4 is present in about 25 to 

30 percent of the population and 

in about 40 percent of all people 

with late-onset Alzheimer’s. People 

who develop Alzheimer’s are more 

likely to have an APOE e4 allele 

than people who do not develop 

the disease. 

Dozens of studies have confirmed 

that the APOE e4 allele increases 

the risk of developing Alzheimer’s, 

but how that happens is not yet 

understood. These studies also help 

explain some of the variation in the 

age at which Alzheimer’s disease 

develops, as people who inherit 

one or two APOE e4 alleles tend to 

develop the disease at an earlier age 

than those who do not have any 

APOE e4 alleles. 

APOE e4 is called a risk-factor gene

because it increases a person’s risk

of developing the disease. However, 

inheriting an APOE e4 allele does

not mean that a person will definitely

develop Alzheimer’s. Some people 

with one or two APOE e4 alleles 

never get the disease, and others who

develop Alzheimer’s do not have any 

APOE e4 alleles.

Using a relatively new approach 

called genome-wide association 

study (GWAS), researchers have 

identified a number of genes in 

addition to APOE e4 that may 

increase a person’s risk for lateonset Alzheimer’s, including BIN1, 

CLU, PICALM, and CR1. Finding 

genetic risk factors like these helps 

scientists better understand how 

Alzheimer’s disease develops and 

identify possible treatments to study. 

Genetic Testing 

Although a blood test can identify 

which APOE alleles a person has, 

it cannot predict who will or will 

not develop Alzheimer’s disease. 

It is unlikely that genetic testing 

will ever be able to predict the 

disease with 100 percent accuracy 

because too many other factors 

may influence its development 

and progression. 

At present, APOE testing is used in

research settings to identify study

participants who may have an increased risk of developing Alzheimer’s. 

This knowledge helps scientists look

for early brain changes in participants 

and compare the effectiveness of 

treatments for people with different 

APOE profiles. Most researchers 

believe that APOE testing is useful 

for studying Alzheimer’s disease risk 

in large groups of people but not 

for determining any one person’s 

specific risk. 

In doctors’ offices and other clinical 

settings, genetic testing is used for 
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Epigenetics: Nature Meets Nurture

Scientists have long thought that genetic and environmental factors interact to 

influence a person’s biological makeup, including the predisposition to different 

diseases. More recently, they have discovered the biological mechanisms for those 

interactions. The expression of genes (when particular genes are “switched” on or 

off) can be affected—positively and negatively—by environmental factors, such as 

exercise, diet, chemicals, or smoking, to which an individual may be exposed, even 

in the womb. 

Epigenetics is an emerging frontier of science focused on how and when particular 

genes are expressed. Diet and exposure to chemicals in the environment, among 

other factors, throughout all stages of life can alter a cell’s DNA in ways that 

affect the activity of genes. That can make people more or less susceptible to 

developing a disease later in life. There is some emerging evidence that epigenetic 

mechanisms contribute to Alzheimer’s disease. Epigenetic changes, whether 

protective, benign, or harmful, may help explain, for example, why one family 

member develops the disease and another does not. Research supported by the 

National Institutes of Health continues to explore this avenue.

The epigenome can “mark” DNA in two ways, both of which play a role in turning genes 

off or on. The first occurs when certain chemical tags called methyl groups attach to the 

backbone of a DNA molecule. The second occurs when a variety of chemical tags attach 

to the tails of histones, which are spool-like proteins that package DNA neatly into 

chromosomes. This action affects how tightly DNA is wound around the histones.

Source: National Human Genome Research Institute, NIH, www.genome.gov
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people with a family history of earlyonset Alzheimer’s disease. However, 

it is not generally recommended for

people at risk of late-onset Alzheimer’s. 

Research Questions

Discovering all that we can about 

the role of Alzheimer’s disease riskfactor genes is an important area of 

research. Understanding more about 

the genetic basis of the disease will 

help researchers:

n Answer a number of basic 

questions—What makes the 

disease process begin? Why do 

some people with memory and 

other thinking problems develop 

Alzheimer’s while others do not? 

Major Alzheimer’s Genetics Research Efforts Underway

As Alzheimer’s disease genetics research has intensified, it has become clear 

that scientists need many genetic samples to make further progress. The National 

Institute on Aging supports several major genetics research programs.

n The Alzheimer’s Disease Genetics Study is gathering and analyzing genetic and 

other information from 1,000 or more families in the United States with two or 

more members who have late-onset Alzheimer’s.

n The Alzheimer’s Disease Genetics Consortium is a collaborative effort of 

geneticists to collect and conduct GWAS with more than 10,000 samples from 

thousands of families around the world with members who do and do not have 

late-onset Alzheimer’s. 

n The Dominantly Inherited Alzheimer Network (DIAN) is an international 

research partnership studying early-onset familial Alzheimer’s disease in 

biological adult children of a parent with a mutated gene.

n The National Cell Repository for Alzheimer’s Disease (NCRAD) is a national 

resource where clinical information and DNA samples are stored and made 

available for analysis by qualified researchers. 

The participation of volunteers is a critical part of Alzheimer’s disease genetics 

research. The more genetic information that researchers can gather and analyze 

from a wide range of individuals and families, the more clues they will have for 

finding additional risk-factor genes. 

To learn more about the Alzheimer’s Disease Genetics Study or to volunteer, 

contact NCRAD toll-free at 1-800-526-2839 or visit www.ncrad.org.
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For More Information

Alzheimer’s Disease Education 

and Referral (ADEAR) Center

P.O. Box 8250

Silver Spring, MD 20907-8250

1-800-438-4380 (toll-free)

www.nia.nih.gov/Alzheimers

The National Institute on Aging’s 

ADEAR Center offers information 

and publications for families, 

caregivers, and professionals on 

diagnosis, treatment, patient care, 

caregiver needs, long-term care, 

education and training, and research 

related to Alzheimer’s disease. 

Staff members answer telephone, 

email, and written requests and 

make referrals to local and national 

resources. The ADEAR website 

provides free, online publications 

in English and Spanish; email 

alerts; a clinical trials database; 

the Alzheimer’s Disease Library 

database; and more.

Additional information about 

genetics in health and disease 

is available from the National 

Human Genome Research 

Institute (NHGRI), part of the 

National Institutes of Health. 

Visit the NHGRI website at 

www.genome.gov.

The National Library of Medicine’s 

National Center for Biotechnology 

Information also provides genetics 

information at www.ncbi.nlm.nih.gov.

Alzheimer’s Association

225 North Michigan Avenue 

Floor 17

Chicago, IL 60601-7633

1-800-272-3900 (toll-free)

1-866-403-3073 (TTY/toll-free)

www.alz.org

Alzheimer’s Foundation 

of America

322 Eighth Avenue, 7th floor

New York, NY 10001

1-866-232-8484 (toll-free)

www.alzfdn.org

n Determine how risk-factor genes 

may interact with other genes and 

lifestyle or environmental factors 

to affect Alzheimer’s risk in any 

one person. 

n Identify people who are at high 

risk for developing Alzheimer’s 

so they can benefit from new 

interventions and treatments 

as soon as possible. 

n Focus on new prevention and 

treatment approaches.
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Glossary

n Allele—A form of a gene. Each person receives two alleles of a gene, one 

from each biological parent. This combination is one factor among many 

that influence a variety of processes in the body. On chromosome 19, the 

apolipoprotein E (APOE) gene has three common forms or alleles: e2, e3, 

and e4. 

n Apolipoprotein E (APOE) gene—A gene on chromosome 19 involved 

in making a protein that helps carry cholesterol and other types of fat in 

the bloodstream. The APOE e4 allele is considered a risk-factor gene 

for Alzheimer’s disease and appears to influence the age at which the 

disease begins. 

n Chromosome—A compact structure containing DNA and proteins present 

in nearly all cells of the body. Chromosomes carry genes, which direct the 

cell to make proteins and direct a cell’s construction, operation, and repair. 

Normally, each cell has 46 chromosomes in 23 pairs. Each biological parent 

contributes one of each pair of chromosomes. 

n DNA (deoxyribonucleic acid)—The hereditary material in humans and 

almost all other organisms. Almost all cells in a person’s body have the same 

DNA. Most DNA is located in the cell nucleus. 

n Gene—A basic unit of heredity. Genes direct cells to make proteins and 

guide almost every aspect of cells’ construction, operation, and repair. 

n Genetic mutation—A permanent change in a gene that can be passed on 

to children. The rare, early-onset familial form of Alzheimer’s disease is 

associated with mutations in genes on chromosomes 1, 14, or 21. 

n Genetic risk factor—A change in a gene that increases a person’s risk of 

developing a disease. 

n Genetic variant—A change in a gene that may increase or decrease a 

person’s risk of developing a disease or condition. 

n Genome-wide association study (GWAS)—A study approach that 

involves rapidly scanning complete sets of DNA, or genomes, of many 

individuals to find genetic variations associated with a particular disease. 

n Protein—A substance that determines the physical and chemical characteristics of a cell and therefore of an organism. Proteins are essential to all cell 

functions and are created using genetic information.

NIH Publication No. 11-6424 June 2011