Alzheimer disease

If you have a positive test result in a gene that can cause familial Alzheimer Disease, other family members may be at risk to have the same genetic change. First-degree relatives (siblings, children, and parents) may have a 50% chance to have the same genetic change. Second-degree relatives (nieces/nephews, aunts/uncles, grandparents, grandchildren, and half siblings) may have a 25% chance to have the same genetic change. Genetic testing is a personal decision. Not everyone at risk for a genetic condition chooses to have genetic testing. Some people will choose to proceed with the testing and some people will not. Each individual must consent to having genetic testing.

Other people with Alzheimer Disease can be found through online support groups. These groups can also help people connect with other caregivers.

Alzheimer’s Disease Education and Referral Center
Alzheimer’s Association

You can also ask your neurologist or other healthcare providers to put you in contact with other families who have Alzheimer Disease who live in your area.

The answer to this question depends on many factors. If a person has a parent with Alzheimer Disease (AD) and no other relatives with AD, the risk for that person to develop AD is around 20% to 25%. Someone with many relatives with AD may have a greater chance to develop Alzheimer Disease. Also, if your parent was found to have a genetic change in PSEN1, PSEN2, or APP that is causing their Alzheimer Disease your risk could be as high as 50%. If you are concerned about your risk and you have a family history of AD, a genetic counselor may be able to help you better understand your risk. Genetic counselors can be found on the National Society of Genetic Counselors website.

The general population lifetime risk to develop dementia symptoms is around 10% to 12%. If a person has a parent, sibling, or child with Alzheimer Disease and no other family history, the risk for that person to develop Alzheimer Disease is around 20% to 25%. The risk value is higher if there is a stronger family history of Alzheimer Disease. Also, if there is a known genetic change in the family that causes Alzheimer Disease, the risk is possibly greater than 25% as well. Each family is different and unique. A genetic counselor or geneticist can help review your family history and determine a more accurate risk for members of your family. Genetic counselors can be found on the National Society of Genetic Counselors website.

Around 75% of the time, Alzheimer Disease is not inherited. The person diagnosed has no family history and no known genetic change that increases the risk for Alzheimer Disease.

25% of people with Alzheimer Disease have the Familial form. People with Familial Alzheimer Disease have a strong family history (more than 2 relatives affected) of Alzheimer Disease and/or in rare cases, a genetic change that increases the risk for Alzheimer Disease.

Alzheimer disease is a disease that affects the brain. It is a common cause of dementia. Common symptoms include memory loss and impaired judgment. The symptoms of dementia progress over time. Most often people are older than 65 years old when they begin noticing symptoms of Alzheimer disease, but in some cases, the diagnosis comes earlier.

As of June 2019, over 20 genes that are thought to lead to a susceptibility to develop Alzheimer Disease (AD) have been identified. The genetic variants identified in these susceptibility genes leads to a small increased risk for AD (less than 2% for most of the identified genes). It is important to realize that having a genetic variant in a susceptibility gene is not the same as having a mutation that actually is known to cause AD. Scientists are still doing active research to understand how the susceptibility genes may interact with genes that are known to cause AD. If you are found to have a change in a susceptibility gene for AD, it is important to know which gene was tested and what our current knowledge is about this gene. You may want to consult with a genetic counselor to understand more about any genetic testing results you have. Genetic counselors can be found on the National Society of Genetic Counselors website.

Genes act as the instructions for the body. We all have two copies of every gene. Patients with early-onset, familial Alzheimer Disease have a gene change (mutation) in one copy of any of these three genes that causes the gene to not work properly. A nonworking copy of one of these three genes leads to an increased risk for Alzheimer disease. If you have a mutation, or genetic change, in one of these genes you will develop Alzheimer disease but it is not possible to predict at exactly what age or how quickly the dementia will progress. When the gene is not working properly, a harmful substance (amyloid beta peptide) can build up in the brain. This substance can clump together to form amyloid plaques. This process has a negative affect on the nervous system, because the build up kills nerve cells.

The PSEN1, APP, and PSEN2 genes cause early onset familial Alzheimer Disease (AD). PSEN1 is responsible for 30% to 70% of early onset familial AD. APP gene causes 10% to 15% of early onset familial AD. PSEN2 causes less than 5% of early onset familial AD. Most genetic changes are small changes that are found through DNA sequence analysis(reading through the gene looking for a spelling mistake). Large deletions (missing pieces of the gene) or duplications (extra pieces of the gene) in the genes are less common.

As of June 2016, four genes have been linked to Alzheimer Disease. Three of these genes are known to cause Alzheimer disease before age 65 when someone has a mutation in one of these genes. They are PSEN1, PSEN2, and APP.

The last gene, APOE is considered a susceptibility gene for Alzheimer disease. This means people who have certain changes in this gene have an increased risk to develop Alzheimer disease but there is no guarantee they will ever develop any symptoms. These people would not expect to show any symptoms before age 65. More research is being conducted to discover more genetic causes for Alzheimer Disease.

Some genetic changes are called "variants of uncertain significance". This means that we found a genetic change that we do not fully understand. We are not quite sure how this genetic change affects the body at this time. It may cause familial Alzheimer Disease and it may not. We need more data and research to make a conclusion about whether or not this change is disease causing. A genetic counselor or geneticist may be able to help explain what this result means for your particular situation. As we learn more, variants of uncertain significance are typically re-classified as either "disease causing" or "not disease causing." It will be important to check in every year with your healthcare provider to see if more has been learned about your variant of uncertain significance. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website. Genetic counselors can be found on the National Society of Genetic Counselors website.

A positive genetic test result means different things depending on which gene was involved. If a genetic change was found in the PSEN1, PSEN2, or APP gene, this means there is a very high chance (95%-100%) that person will develop Early Onset Alzheimer disease (before age 65). This result may or may not change your medical management. Other relatives can be tested for the same genetic change to assess their risk for Alzheimer disease should they wish. If a genetic change was found in APOE showing you have either 1 or 2 e4 alleles, this increases your chance to develop Late Onset Alzheimer disease (over age 65) although there is no way to know for sure whether or not you will ever develop Alzheimer disease. Anyone with a positive Alzheimer disease genetic testing result is recommended to meet with a genetic counselor. To locate a genetic counselor near you visit www.nsgc.org.

A negative genetic test result means that the laboratory analyzed the DNA and found no genetic changes that increase the risk for Familial Alzheimer disease. This result has different implications depending on who was tested.

Alzheimer Disease (AD) is a common cause of dementia. It begins with general forgetfulness, but this can lead to memory loss and impaired judgment. People with more advanced symptoms can feel lost or confused by regularly visited places and common activities. People with AD may lose the ability to live independently. Changes to behavior are reported as well, and people may react inappropriately in social situations. Impatience, agitation, and withdrawal are described as symptoms. Symptoms of Alzheimer Disease can start as mild but typically progress over time.

After being diagnosed with Alzheimer disease, the first step is to find a neurologist who has experience treating others with Alzheimer disease and/or dementia. There are various Alzheimer Disease Centers throughout the United States. These centers have experts in Alzheimer disease who also do research related to Alzheimer disease. To see if there is a center near you, click here.

There is currently no cure for AD so symptoms are treated as they occur. There are medications that have been proven to help those with AD. The first drug discovered is tacrine but this can hurt the liver. Newer drugs have been discovered that do not damage the liver. These are
donepezil (Aricept®), rivastigmine (Exelon®), and galantamine. In moderate to severe Alzheimer Diseae memantine has worked. Antidepressant medication may also be recommended for people with AD who have depression or other mental health concerns.

It is not recommended to test minors for gene changes that cause Familial Alzheimer Disease. The youngest age at which a person can be tested is 18 years of age. Waiting until young adulthood to pursue genetic testing allows for the person to make an informed decision for himself or herself. Some people choose to be tested and some people choose not to be tested. It is important a person is able to make that decision for themselves.

The question of whether or not there is variable expression or incomplete penetrance in familial Alzheimer Disease is dependent on which gene has a change (mutation) that causes it. There are three genes that cause early onset Alzheimer Disease: PSEN1, PSEN2, and APP. There is another gene, APOE, that is associated with an increased risk for late onset Alzheimer Disease.

PSEN1 gene: Familial AD caused by mutations to the PSEN1 gene has nearly complete penetrance. This means that nearly all people with a disease-causing change in this gene will develop AD.

PSEN2 gene: Familial AD caused by mutations in the PSEN2 gene has around 95% penetrance. This means that 95% of people with a disease-causing change in this gene will develop AD. This means 5% of people who have a change in this gene will not develop symptoms of Alzheimer Disease.

APP gene: Familial AD caused by mutations in the APP gene does not have complete penetrance although the exact numbers are not known at this time. This means not everyone will an APP disease causing change will develop Alzheimer’s disease although the chances are very high.

APOE gene: Having a change to APOE does not confirm or rule out that a person will have Alzheimer Disease. Certain changes to APOE (mainly APOe4 allele) can raise the risk to develop Alzheimer Disease. There is no way to accurately predict whether someone with an APOe4 allele will develop Alzheimer disease or not. This is why genetic testing of the APOE gene is not recommended at this time.

All of the genes can show variable expression. This means that different people with the same genetic change will show different symptoms at different ages. Even within the same family people can develop Alzheimer Disease at different ages. In some people the disease progresses quickly and in others it progresses more slowly. Some people present with different symptoms than other family members.

As of June 2016, Alzheimer Disease is not on the newborn screen. It is unlikely Alzheimer Disease will be added to newborn screening unless a cure or effective treatment is found. In general, newborn screening only screens for childhood onset conditions.

There are many testing options for Alzheimer Disease. If there is a known mutation in a family, targeted testing can be ordered. With targeted testing, the laboratory will only look for one specific genetic change instead of checking the entire gene. This is generally the least expensive option offered by testing companies.

There are different test options for people with no known mutations in the family as well. Analyzing the PSEN1, PSEN2, APP and APOE genes may provide you with more information on your risk to develop Alzheimer Disease. The genetic testing approach will be influenced based on your personal medical and family history. There are benefits/ risks/ limitations to different types of genetic testing, and it is important to have genetic counseling from a qualified healthcare provider to aid in this decision making process.

As of June 2019 there are multiple research studies being conducted on Alzheimer Disease. ClinicalTrials.gov can provide up-to-date information on research happening now. You can also learn about current research news through the National Institute on Aging (https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-genetics-fact-sheet#research). Some research will be focused on Alzheimer Disease in general, but there may be research specific to Familial Alzheimer Disease as well.

As of June 2016, there is no treatment that can cure or prevent Alzheimer Disease. Certain symptoms do have treatments available. Some drugs have been shown to improve symptoms of depression, behavioral changes, or cognitive decline. Donepezil, rivastigmine, galantamine, and memantine have been used in patients with Alzheimer Disease. Your neurologist can help you select the right medication for you based on your symptoms. Sometimes vitamins and other over the counter remedies are recommended.

Prenatal testing and preimplantation genetic diagnosis (PGD) is available for Familial Alzheimer Disease if the genetic change (mutation) present in the family is known. PGD allows for parents to only implant embryos into the mother’s uterus that do not have the genetic mutations that cause Familial Alzheimer Disease. PGD is still a very costly procedure, and it is not guaranteed to lead to pregnancy every time.

With prenatal diagnosis, the baby’s DNA is tested during the pregnancy to determine whether the child has the gene mutation that causes Familial Alzheimer Disease. This can be done through a procedure called chorionic villi sampling (11-13 weeks of pregnancy) or amniocentesis (16-23 weeks of pregnancy). This practice is less commonly used for adult onset conditions like Familial Alzheimer Disease, especially if the genetic change only increases the risk slightly to develop Alzheimer Disease as an adult.

Twenty-five percent of all Alzheimer Disease is thought to be Familial. Familial means more than 2 closely related family members are affected with Alzheimer Disease. Familial Alzheimer Disease is not always have symptoms that start at an early age. Familial Alzheimer Disease caused by genetic changes to the APOE gene causes symptoms at a later age. This means that generally the onset of symptoms is after 65 years old. Up to 98% of people with Familial Alzheimer Disease have later onset of symptoms. Less than 2% of people with familial Alzheimer syndrome have early onset of symptoms. Most cases of Familial Late Onset Alzheimer Disease cannot be explained by a single gene.

Often, there is not a single genetic cause that we can identify. Genes seem to play a role in why a person has Alzheimer disease, but we are not always able to find a genetic cause. Around 25% of cases seem to be due to familial Alzheimer disease. These families have multiple people diagnosed with Alzheimer disease.

The other 75% of the time, Alzheimer disease does not appear to be the familial form. It is in the sporadic form. Sporadic means it is the first case of Alzheimer disease in a family. The cause of sporadic Alzheimer disease is not well understood. Sporadic Alzheimer Disease is likely caused by a combination of genetic and environmental factors.

In rare cases, there is a strong family history of early onset Alzheimer disease. In the early onset form, people are diagnosed with Alzheimer disease before the age of 65. There are three known genes that cause the early onset familial form of Alzheimer disease. The genes are PSEN1, APP, and PSEN2 and genetic testing is available.

People who have Down syndrome have an increased risk to develop Alzheimer Disease in their lifetime, but it is not believed that their relatives without Down syndrome are at any increased risk. Researchers believe that people who have Down syndrome are at increased risk because they have three copies of the APP gene instead of two. Most people have 23 pairs of chromosomes resulting in 46 total chromosomes. People who have Down Syndrome have 47 total chromosomes because they have an extra copy of chromosome 21. The APP gene is found on chromosome 21. People who have Down Syndrome have 3 copies of the APP gene instead of 2. Their relatives do not have this extra copy of the APP gene so they are not believed to be at increased risk.

Once a person develops symptoms of Alzheimer disease, they usually live 8 to 10 years. This varies from person to person. Some people who have Alzheimer disease will live more than ten years and others will live less than eight years. People with Alzheimer disease most often pass away from pneumonia and poor nutrition. Regular follow up with your neurologist and other healthcare specialists can ensure the person who has Alzheimer Disease is getting proper medical care and treatment. When AD becomes severe, a caregiver or living in an assisted living facility is helpful to ensure the person who has AD is being cared for appropriately.

Around 75% of the time, Alzheimer Disease (AD) is not inherited. 25% of the time Alzheimer’s disease can be inherited. This is called familial AD. There are at least four known genes that can cause familial, or inherited Alzheimer Disease.

We all have two copies of every gene, including two of the PSEN1 and PSEN2 genes that can cause familial AD. We inherit half of our genetic information from our mom and half from our dad; so one copy of each gene is inherited from our mother and the other from our father. If a parent has familial AD caused by PSEN1 or PSEN2, there is a 50% chance that any of their children will also have AD. This is called autosomal dominant inheritance. Only one copy of the gene needs to be not working (mutated) to lead to symptoms of Alzheimer Disease.

We also have two copies of the APP gene. One of our APP genes is inherited from our mother, and the other is inherited from our father. Sometimes AD caused by APP gene changes is inherited in a dominant fashion like PSEN1 and PSEN2.

Other times, both copies of the APP gene must have genetic changes (mutations) for someone to have symptoms of AD. In this case, if both parents have 1 APP gene mutation, there is a 25% that any child will have symptoms of AD. There is also a 25% chance that any child will inherit neither parent’s APP mutation. There is a 50% chance that any child will only inherit one APP gene mutation and be a "carrier" like their parents. Someone with AD caused by APP gene mutations cannot have a child with Alzheimer Disease unless their partner also has at least one APP gene mutation.

There are multiple ways to help the Alzheimer Disease community by donating money. The NIH: National Institute on Aging provides information about the projects they are conducting on Alzheimer Disease (https://www.nia.nih.gov/alzheimers/news). You should be able to contact a study coordinator and ask about donating to a particular study should you wish. You can also donate to a support group like the Alzheimer’s Association (www.alz.org),

Not everyone is a good candidate for genetic testing for Alzheimer Disease. Molecular genetic testing is used in some cases of Familial Alzheimer Disease. Genetic testing is not required to assess whether Alzheimer Disease is familial or not, but it can help to fully confirm it. Analyzing the PSEN1, PSEN2, APP and APOE genes may provide you with more information on your risk to develop Alzheimer Disease. There are numerous genetic testing laboratories that offer testing for familial Alzheimer Disease. There are multiple types of tests to choose from. A genetic counselor can assist you as you decide what type of genetic testing is right for both you and your family. You can locate a genetic counselor at http://nsgc.org/p/cm/ld/fid=164.

You can find a doctor that specializes in Alzheimer Disease through the NIH’s Alzheimer’s Disease Education and Referral Center website (https://www.nia.nih.gov/alzheimers/alzheimers-disease-research-centers).

A genetic counselor can help to further explain familial Alzheimer Disease and answer any questions you have. Genetic counselors can be found on the National Society of Genetic Counselors website.

ClinicalTrials.gov can provide up-to-date information on research being conducted. You can also learn about current research news through the National Institute on Aging (https://www.nia.nih.gov/alzheimers/publication/alzheimers-disease-genetics-fact-sheet#research). They also provide information about how to get yourself involved if you wish (https://www.nia.nih.gov/alzheimers/volunteer). Some research will be focused on Alzheimer Disease in general, but there may research specific to familial Alzheimer Disease as well.

Alzheimer disease is a rather common diagnosis. Alzheimer disease is the most common cause of dementia in North America and and Europe. About 5% of people over 70 years old have a diagnosis of Alzheimer disease. Around 2.4 million to 4.5 million people living in the U.S. have Alzheimer disease.

The Alzheimer’s Association provides patients with resources to help them with their finances. You can learn about how to get the most out of your insurance but also it can help you prepare for the future. People who have Alzheimer Disease usually qualify for disability. Click here to learn more about applying for disability if you or a loved one has Alzheimer Disease.

A clinical diagnosis of Alzheimer Disease can be made from a patient’s symptoms. In 80-90% of cases, the diagnosis of Alzheimer Disease is correct. Signs of Alzheimer Disease include slowly progressive dementia and a brain MRI finding called gross cerebral cortical atrophy. Some people have a spinal tap done to check the levels of certain proteins in the cerebrospinal fluid which protects the brain and spinal cord. These proteins are called A-beta amyloid 42 and tau. The most accurate way to diagnose someone with Alzheimer Disease is to perform an autopsy after death. After a person with Alzheimer Disease passes away, their brain can be checked to look for amyloid plaques, tangles, and amyloid angiopathy which are abnormal findings in the brain. These findings prove the person had Alzheimer Disease.

Genetic testing for familial Alzheimer most often will be done on a blood sample. Some labs may allow for a saliva sample to be submitted, but this is not usually the preferred option for many labs. Solid tissue from a biopsy can also be used for testing, but a blood sample is generally the best option. You can find updated information on what sample a lab will accept at GeneTests.org.

People with Down syndrome do have an increased risk to develop Alzheimer Disease in their lifetime. Some people who have Down Syndrome will show some evidence of the disease after age 40. As of June 2016, researchers believe that this is due to people with Down syndrome having three copies of the APP gene instead of two. People with Down syndrome have three copies of chromosome 21, and the APP gene is located on chromosome 21.

As of June 2016, four genes have been linked to Alzheimer Disease. The APP, PSEN1, PSEN2, and APOE genes have been associated with Alzheimer Disease. Genetic changes (mutations) to the APP, PSEN1, and PSEN2 genes cause Alzheimer Disease. Genetic changes to the APOE gene can raise the chances that someone will develop Alzheimer Disease, but it is not greatly increased risk. More research is being conducted to discover more genetic causes for Alzheimer Disease.

Alzheimer Disease is also referred to as Alzheimer dementia, Alzheimer sclerosis, Alzheimer syndrome, Alzheimer-type dementia, and presenile and senile dementia. Alzheimer Disease is often abbreviated to AD.

There are good support groups for people with Alzheimer Disease and for the people that care for them. Alzheimer’s Association is a wonderful resource that has information for those who are affected, their children, caregivers, and every member of the family in between. They also have local events in certain areas. Visit www.alz.org for more information.

Another great resource is the National Institute of Health Alzheimer Disease Education and Referral Center. Visit www.nia.nih.gov/alzheimers to learn more.

As of June 2016, there are no known environmental causes of Alzheimer Disease. Environmental factors probably play a role in whether someone develops the disease, but we do not know about any specific causes with a large impact at this time.

There is a range in when symptoms of Alzheimer Disease present. Most often people are older than 65 years old when they begin noticing symptoms of Alzheimer Disease, but in some cases, the symptoms appear earlier. Typically, it is described as “early onset” if the diagnosis is before age 65. Less than 5% of cases are thought to be early onset. The other 95% is late onset. Any diagnosis after age 65 is considered late onset. Sometimes it is difficult to figure out exactly when symptoms started.

There are many diagnoses to consider when a person presents with dementia. Frontotemporal dementia, Picks disease, Parkinson disease, diffuse Lewy body disease, Creutzfelft-Jakob, and CADASIL are important common differential diagnoses for people presenting with symptoms of dementia.

There can be other reasons for a person to have symptoms mirroring dementia too. These other causes include depression, drug abuse, thyroid disease, improper nutrition (B12 and thiamine vitamin deficiency specifically), slight build up of water build up in the brain (hydrocephalus) and disease of the central nervous system.