What are the other Names for this Condition? (Also known as/Synonyms)

• Early-Onset Autosomal Dominant Alzheimer Disease
• Early-Onset Familial Alzheimer Disease (EOFAD)
• Early-Onset Familial Autosomal Dominant Alzheimer Disease

What is Familial Alzheimer Disease? (Definition/Background Information)

• Familial Alzheimer Disease is a form of Alzheimer disease (AD) that develops before the age of 65
• It is diagnosed in families that have more than one member with AD (usually multiple persons in more than one generation) in which the age of onset is consistently before age 60 and often between the ages of 30 and 60 years
• In general, AD is a degenerative disease of the brain that causes gradual loss of memory, judgement, and the ability to function socially

There are three subtypes of early-onset familial AD which are each associated with changes (mutations) in unique genes:

• Alzheimer disease, type 1 is caused by mutations in the APP gene
• Alzheimer disease, type 3 is caused by mutations in the PSEN1 gene
• Alzheimer disease, type 4 is caused by mutations in the PSEN2 gene

All subtypes are inherited in an autosomal dominant manner. There is no cure for AD. Treatment is supportive and based on the signs and symptoms present in each person.

(Source: Familial Alzheimer Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Familial Alzheimer Disease? (Age and Sex Distribution)

• Familial Alzheimer Disease is a rare inherited disorder. Typically, the presentation of symptoms occur between the period 30-60 years
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Familial Alzheimer Disease? (Predisposing Factors)

• A positive family history is an important risk factor, since Familial Alzheimer Disease is inherited

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Familial Alzheimer Disease? (Etiology)

Familial Alzheimer Disease is inherited in an autosomal dominant manner.

• This means that to be affected, a person only needs a change (mutation) in one copy of the responsible gene in each cell. In some cases, an affected person inherits the mutation from an affected parent
• Other cases may result from new (de novo) mutations in the gene
• These cases occur in people with no history of the disorder in their family
• A person with this condition has a 50% chance with each pregnancy of passing along the altered gene to his or her child

(Source: Familial Alzheimer Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Familial Alzheimer Disease?

The signs and symptoms of Familial Alzheimer Disease may include:

• Memory loss/problems
• Difficulty performing daily activities, difficulty reading, sleeping
• Agitation
• Depression
• Anxiety 
• Mental retardation 

How is Familial Alzheimer Disease Diagnosed?

• Familial Alzheimer Disease is diagnosed in families that have more than one member with AD in which the age of onset is before age 60 to 65 years
• Genetic testing and identification of a mutation in one of the implicated genes (PSEN1, APP, or PSEN2) in an affected family member can assist in confirming the diagnosis
• Not all families with early-onset, autosomal dominant Alzheimer disease are found to have mutations in one of the three known genes; therefore there may be other genes involved that have not yet been reported

(Source: Familial Alzheimer Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Familial Alzheimer Disease?

The complications of Familial Alzheimer Disease may include:

• Alzheimer’s disease is the most common cause factor for dementia. Dementia is a type of disorder accompanied by a collection of symptoms that indicate brain impairment and loss of brain function
• Since AD is a progressive disorder, it can create difficulties in the life of the individual, and their family members 
• As symptoms worsen, it becomes more and more difficult for those affected by the condition to carry out even simple, everyday tasks. They are usually unable to live on their own

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Familial Alzheimer Disease Treated?

• Unfortunately, there is no cure for Alzheimer disease in general; however, there are medications that may assist in temporarily helping with memory and thinking problems, such as Exelon, Galantamine, and Aricept
• Physical and occupational therapy can be helpful in managing problems with walking and activities of daily living
• Depression and seizures may be treated with appropriate medications

(Source: Familial Alzheimer Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Familial Alzheimer Disease be Prevented?

Currently, Familial Alzheimer Disease may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Familial Alzheimer Disease? (Outcomes/Resolutions)

• The prognosis of Familial Alzheimer Disease is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Familial Alzheimer Disease:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/diseases-conditions/rare-disorders/