Patient Test Information


Also known as:

PS1; PS-1; Presenilin 1 Gene; S182

Formal name:

PS1 or PSEN1 Genetic Mutation Analysis

Related tests:

APOE Genotyping; Tau/AB42; PSEN2; Amyloid Precursor Protein (APP)

Why Get Tested?

To screen for a rare mutation in the PSEN1 gene known to be associated with early onset familial Alzheimer disease (EOFAD, also called Alzheimer disease type 3 or AD3)

When to Get Tested?

When you are an adult who has symptoms of dementia and a strong family history of Alzheimer disease that begins before age 60-65 or if you are an asymptomatic adult with a family member who has early onset Alzheimer disease and an identified PSEN1 genetic mutation

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?


How is it used?

PSEN1 genetic mutation analysis is used to screen asymptomatic or symptomatic adults who have a strong family history of early onset Alzheimer disease (EOFAD, also called Alzheimer disease type 3 or AD3), especially when a specific PSEN1 mutation has been identified in other family members. It may be used to aid in the differential diagnosis of EOFAD versus other forms of early onset dementia but usually only in those with a family history of AD3. Appropriate genetic counseling may be pursued to assess the risk of either parent having and passing on a PSEN1 mutation. However, PSEN1 testing is rarely ordered prenatally because an amniocentesis is required and because it is not common practice to test prenatally for adult-onset diseases.

The PSEN1 test is not useful as a screen for the general population or for those who have late onset AD.

When is it ordered?

This test may be ordered when a person develops symptoms associated with Alzheimer disease before 65 years of age. PSEN1 mutation analysis may also be ordered when an asymptomatic adult has a strong family history of early onset Alzheimer disease, especially when there are multiple family members over several generations who have had or were thought to have had AD3.

Very rarely, PSEN1 testing may be ordered prenatally when there are documented affected family members and a specific PSEN1 gene mutation has been identified in a family member. It is not common practice to test prenatally or to test children for adult-onset diseases.

What does the test result mean?

If a person has one of the PSEN1 mutations, it is highly likely that the person will eventually develop AD3, usually at a similar age to other affected family members. The penetrance of the gene (i.e., the symptoms, the severity, and the rate of progression) can vary from individual to individual. Since it is a dominant gene, each child will have a 50% chance of having the PSEN1 mutation passed on to them.

If the PSEN1 genetic mutation analysis is negative, it is still possible that the person has AD3 because the mutation is not able to be identified by the existing testing method and may be due to a different mutation of the PSEN1 gene or a mutation of another gene yet to be identified.

Is there anything else I should know?

The PSEN1 genetic mutation is almost exclusively family-related and is not associated with late onset AD. A few cases of PSEN1 genetic mutation will show up without a strong family history because of "alternate" paternity, new mutations, or because a parent died before symptoms developed so this element of the family history was unknown.

The PSEN1 test is a relatively new, comparatively expensive test that has limited use and is still rarely ordered. It is performed in only a few laboratories, so if a health practitioner recommends the test, the blood sample will need to be sent to a reference laboratory and results may take awhile to return. As with many new testing modalities, the analysis may be costly and is often not covered under most insurance plans.

What is being tested?

This test looks for mutations in the PSEN1 gene sequence that have been associated with early onset familial Alzheimer disease (EOFAD, also called Alzheimer disease type 3 or AD3).

Although most Alzheimer disease (AD) cases start after the age of 65, about 5-10% of cases begin in people younger than 65 years of age. Much of this early onset AD is familial - it runs in family lines and is caused by a genetic mutation. So far, there have been three rare gene mutations that have been identified as being associated with AD3: PSEN1, PSEN2, and amyloid precursor protein (APP).

PSEN1 is the most common of these gene mutations and is thought to cause about 30% to 70% of the cases of AD3. Since PSEN1 is a dominant gene (autosomal dominant), it only takes one mutated copy, inherited from either the mother or father, to lead to the development of AD3.

Why PSEN1 mutations are associated with AD3 is not completely understood. It is thought that the normal role of the PSEN1 gene is to make the presenilin 1, a protein used in the development of the brain and spinal cord. Presenilin 1 also works with other enzymes to cut certain proteins into smaller pieces (amyloid beta peptide). A mutation of PSEN1 produces an abnormal presenilin 1 protein that no longer functions properly, resulting in a breakdown of this process. This breakdown lends itself to increased production of a longer, stickier configuration of the amyloid beta protein, which is toxic to the nervous system and eventually forms the characteristic amyloid plaques seen with AD.

So far, more than 150 mutations of the PSEN1 gene have been identified in a limited number of different family lines worldwide. The large number of mutations suggests that there may be additional mutations not yet known; thus, the PSEN1 test will not identify every person who has a PSEN1 mutation.

The analysis is made easier if a specific PSEN1 mutation has already been identified in a person's family line. The PSEN1 genetic mutation analysis is a relatively new test and is offered by a limited number of laboratories.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

  1. My father has been diagnosed with early onset Alzheimer disease (AD3). Can my doctor tell if my father has a genetic mutation without a blood test?

    No, the symptoms for AD3, sporadic early onset AD, and late onset AD are the same except for the age of onset. You cannot tell whether someone has a genetic mutation just by looking at their perceived abnormal daily living activities. If there is a strong family history of early onset AD, especially if another family member has been diagnosed with a genetic mutation, your doctor may suspect a genetic problem that may be confirmed by a blood test.

  2. Are there any other genetic tests that will diagnose AD?

    The other genes that have mutations associated with AD3 are PSEN2 and APP (amyloid precursor protein). Testing is available, but it should be noted that these gene mutations are very rare and have only been identified in a very small number of specific family lines.