Genetic and Hereditary Risk Factors for Alzheimer's Disease

As the incidence of Alzheimer’s disease continues to rise, so too does the push for medical science to discover the cause of the disease. Is it genetic? If so, what are the hereditary risk factors of Alzheimer’s disease?

This article looks at the genetic and hereditary risk factors of Alzheimer’s disease and how genes influence late- and early-onset Alzheimer's.

patient talking to doctor
Preparing for your conversation with your doctor helps you take more control during your appointment. It's no longer about the paternalistic doctor. It's about a responsible you.

ThomasBarwick / Getty Images

Genetic and Hereditary Risk Factors

As new discoveries develop in Alzheimer’s research, scientists are beginning to ascertain pieces to the puzzle concerning the cause. Many scientific discoveries are pointing to a strong link between Alzheimer’s disease, genetics, and hereditary risk factors.

Alzheimer’s disease (AD) is becoming known as a complex “multifactorial” disorder. This means that even though scientists are unaware of exactly how Alzheimer’s begins, they believe it is caused by environmental circumstances combined with genetic factors (another way of describing a multifactorial disorder).

Alzheimer’s Characteristics

To have a solid understanding of how genetics affects Alzheimer’s disease, it’s important to be aware of some of the basic facts about the disease process. What scientists know is that Alzheimer’s is characterized by the development of abnormal proteins such as the following:

  • Amyloid plaques: a hallmark sign of Alzheimer’s disease in the brain. Amyloid plaques are abnormal protein fragments (called beta-amyloids) that clump together and form plaques that are toxic to neurons (nerve cells).
  • Neurofibrillary tangles (tau tangles): abnormal structures in the brain caused by Alzheimer’s disease that involve a type of protein called tau. Normally, tau helps to support structures called microtubules. Microtubules function to transport nutrients from one part of the nerve cell to another. But, in Alzheimer’s disease, the microtubules collapse (due to the malformation of its structure) and are no longer able to carry nutrients required for normal neuron function.

Both amyloid plaques and neurofibrillary tangles interfere with the ability of nerve impulses to travel from one neuron (brain cell) to another. Eventually, both types of abnormal proteins (tau tangles and beta-amyloid) cause death to the neurons. This results in memory loss, disruption in thinking skills, and eventually leads to dementia.

There are essentially two types of Alzheimer’s disease, including early-onset and late-onset Alzheimer’s. Each type of AD involves a genetic cause or a genetic predisposition (risk).

Genetics 101

To thoroughly understand the genetic and hereditary risk factors of Alzheimer’s disease, it’s important to be familiar with some common genetic terms, these include:

  • Hereditary disease: can be passed on from one generation to another
  • Genetic disease: may or may not be hereditary, but a genetic disease is always the result of a change in the genome
  • Genome: a person’s complete DNA set which is contained in every cell of the body. A genome is like a blueprint that contains instructions for making and maintaining the function of every cell (organ and tissue) in the body.
  • Gene: a segment of inheritable information made up of DNA that is passed down from parents to their children. Genes have a fixed position, organized as packaged in units called chromosomes. They instruct the cell on jobs such as how to function, how to make proteins, and how to repair itself. 
  • Protein: made by following the instructions from genetic information—all cells in the body require protein to function. Protein determines the chemical structure (characteristics) of the cell, and cells make up tissues and organs in the body. Therefore, protein determines the characteristics of the body.
  • DNA (deoxyribonucleic acid): a chemical that makes up the double helix molecule that encodes genetic information. DNA has 2 important properties: it can make copies of itself and it can carry genetic information.
  • Chromosome: a compact structure (contained inside the nucleus of the cell) involving long pieces of DNA that are tightly coiled into a package. This allows DNA to fit inside the cell. The chromosomes contain thousands of genes which function to carry genetic information. Humans have a total of 46 chromosomes (23 from the father and 23 from the mother). With two sets of chromosomes, the offspring inherits two copies of each gene (including one copy from each parent).
  • Genetic mutation: a permanent change in a gene that can cause illness and can be passed down to the offspring. Early-onset familial Alzheimer’s disease involves gene mutations on specific chromosomes, number 21, 14, and 1.
  • Gene variant: every human’s genome (complete DNA set) contains millions of these. Variants contribute to individual characteristics (such as hair and eye color). A few variants have been linked with disease, but most variants are not fully understood regarding the impact they have.
  • Apolipoprotein E (APOE) gene: a gene that is involved in making a protein that helps carry cholesterol (and other fats) and vitamins throughout the body (including the brain). There are three types of APOE genes; the APOE4 gene variant presents a major known risk factor for late-onset Alzheimer’s disease. It is located on chromosome 19.

How Genes Influence Alzheimer’s

Genes literally control every function in each of the human body’s cells. Some genes determine the characteristics of the body, such as a person’s eye or hair color. Others make a person more likely (or less likely) to get a disease.

Several genes have been identified that are linked to Alzheimer's disease. Some of these genes can increase the risk of getting Alzheimer’s (these are called risk genes). Other genes, most of which are rare, guarantee that a person will develop a disease. These are called deterministic genes.

Precision Medicine

Scientists are working diligently to identify genetic mutations for Alzheimer’s disease in the hopes of discovering individualized methods of preventing or treating the disorder. This approach is referred to as “precision medicine,” because it examines individual variability of a person’s genes, as well as the person’s lifestyle (diet, socialization, and more) and environment (exposure to pollutants, toxic chemicals, brain injury, and other factors).

Genetic Mutations and Disease

Illnesses are commonly caused by genetic mutations (a permanent change in one or more specific genes). In fact, there are over 6,000 genetic disorders characterized by mutations in the DNA, according to the Victoria State Government. 

When a genetic mutation that causes a specific illness is inherited from a parent, the person who inherits that gene mutation will often get the disease. 

Examples of diseases caused by a gene mutation (inherited genetic disorders) include:

It's important to note that early-onset familial Alzheimer’s disease caused by a gene mutation is rare and comprises a very small segment of those who are diagnosed with AD.

Genetics and Late-Onset

Late-Onset Alzheimer’s Disease

One gene that has been strongly linked with a gene variant (change) that increases the risk of late-onset Alzheimer’s disease is the APOE4 gene. When a change in a gene increases the risk of a disease, rather than causing it, this is referred to as a genetic risk factor. Although it’s not clear exactly how APOE4 increases the risk of getting AD, scientists believe that the risk is linked to a combination of factors—including environmental, lifestyle, and genetic factors.  

Environmental factors involve things like smoking or exposure to other types of toxic substances. Lifestyle factors involve diet, exercise, socialization, and more. When it comes to genetic factors, researchers have not found a specific gene that directly causes the late-onset form of Alzheimer’s disease, but they do know that the APOE4 gene increases the risk of getting late-onset Alzheimer’s.

What Is an Allele?

An allele is a variant form of a gene. At conception, an embryo receives an allele of a gene from the mother and an allele of a gene from the father. This combination of alleles is what determines genetic characteristics such as the color of a person’s eyes or hair. The APOE gene is located on chromosome number 19 and has three common alleles, including:

  • APOE-e2: a rare allele that is thought to provide some protection against Alzheimer’s
  • APOE-e3: an allele that is thought to be neutral as far as the risk of Alzheimer’s disease is concerned, this is the most common allele of the APOE gene
  • APOE-e4: the third allele, which has been identified as increasing a person’s risk of getting late-onset Alzheimer’s. A person can have zero, one, or two APOE4 alleles (inheriting none from their parents, one allele from one parent, or one allele from each parent).

It’s important to note that not everyone with the APOE4 allele will necessarily get Alzheimer’s. This may be because there are many factors involved—in addition to the genetic link to the disease—such as environmental and lifestyle factors.

Therefore, a person who inherits the APOE4 allele of the gene is not assured of getting Alzheimer’s disease. On the other hand, many people who get diagnosed with AD, do not have the APOE4 form of the gene.

Other Genes Linked with Late-Onset Alzheimer’s 

According to Mayo Clinic, several other genes in addition to the APOE4 gene have been linked with an increased risk of late-onset Alzheimer’s. These include:

  • ABCA7: the exact way it is involved in an increased risk of AD is not well known, but this gene is thought to play a role in how the body utilizes cholesterol
  • CLU: plays a role in helping to clear beta-amyloid from the brain. The body’s normal ability to clear amyloid is vital to the prevention of Alzheimer’s.
  • CR1: this gene produces a deficiency of protein, which may contribute to inflammation of the brain (another symptom strongly linked with Alzheimer’s)
  • PICALM: this gene is involved in the method that neurons communicate with each other, promoting healthy brain cell functioning and effective formation of memories
  • PLD3: the role of this gene is not well understood, but it has been linked with a significant increase in the risk of AD
  • TREM2: this gene plays a role in regulating the brain’s response to inflammation. Variants of TREM2 are thought to increase the risk of AD.
  • SORL1: variations of this gene on chromosome 11 may be linked with Alzheimer's

Genetics and Early-Onset

The second type of Alzheimer’s disease, called early-onset Alzheimer’s, occurs in people in their mid-30s to mid-60s.

One form of early-onset Alzheimer’s disease—called early-onset familial Alzheimer’s disease (FAD)—is inherited from a parent by what is referred to as an autosomal dominant pattern. This means that it only takes one parent to pass down the defective copy of the gene for a child to develop the disorder. The gene mutation that causes early-onset FAD is one of several mutations occurring on chromosomes 21, 14, and 1.

When a child’s mother or father carries the genetic mutation for early-onset FAD, the child has a 50% chance of inheriting the mutation, according to the National Institute on Aging. Then, if the mutation is inherited, there is a very strong likelihood of the child growing up to develop early-onset familial Alzheimer’s disease. 

Note, although early-onset Alzheimer’s is said to occur in 5% of all instances of AD, according to Mayo Clinic, the genetic form of early-Alzheimer’s (early-onset FAD) occurs in just 1% of those diagnosed with the disease. In other words, some cases of early-onset Alzheimer’s are not genetically linked.

Early-onset FAD can be caused by one of several gene mutations on chromosome 21, 14, and 1, involving the genes called:

  • Amyloid precursor protein (APP)
  • Presenilin 1 (PSEN1)
  • Presenilin 2 (PSEN2)

These mutations all cause the formation of abnormal proteins and are thought to have a role in the production of amyloid plaques—a hallmark symptom of Alzheimer’s disease.

Genetic Testing

Genetic testing is often performed before Alzheimer’s research studies are conducted. This helps scientists to identify people with gene mutations or variations linked with Alzheimer’s. This also helps scientists identify early changes in the brain in study participants, in the hopes of enabling researchers in developing new Alzheimer’s prevention strategies.

Since there are so many factors other than genetics that play into whether a person will get late-onset Alzheimer’s or not, genetic testing does not very accurately predict who will be diagnosed with AD and who will not. 

For this reason, it’s not advisable for the general population to seek out genetic testing solely for this reason. It may pose as more of a needless worry than an actual prediction of risk.

A Word From Verywell

It’s important to talk to your healthcare provider to get sound medical advice before making a decision to pursue genetic testing. The results of genetic testing for Alzheimer’s disease are difficult to interpret. There are also many companies that aren't medically competent in performing genetic testing or that don't offer sound advice about the interpretation of genetic tests.

If a person does have the genetic predisposition for AD and gets genetic testing, it could impact her eligibility to get certain types of insurance, such as disability insurance, life insurance, or long-term care insurance. Speaking with your primary doctor is the best first step in ensuring you are considering your options before pursuing genetic testing.

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

By Sherry Christiansen
Sherry Christiansen is a medical writer with a healthcare background. She has worked in the hospital setting and collaborated on Alzheimer's research.