At a glance

Also known as

PS1; PS-1; AD3; Presenilin 1; S182

Why get tested?

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

When to get tested?

If you are an adult who has symptoms of dementia and a strong family history of early onset Alzheimer’s disease (AD that begins before age 60-65 years) or if you are an adult with no symptoms but with an identified PSEN1 genetic mutation (and EOFAD) in your family. Prior to testing, appropriate genetic counselling should be provided.

Sample required?

A blood sample drawn from a vein in your arm

Confused about genetics?

See our Genetics Information page

Test preparation needed?

What is being tested?

This test looks for mutations in the PSEN1 gene, which have been associated with early onset familial Alzheimer's disease (EOFAD). Although most Alzheimer's disease (AD) starts after the age of 65 (late onset), about 5-10% of cases of the disease begin in people under 65 years of age. Much of this early onset AD is inherited - it runs in families and is caused by a genetic mutation. There have been mutations identified in three genes so far that are associated with EOFAD; all are very rare. Of these, PSEN1 is the most common and is thought to cause about 30-70% of the cases of EOFAD. The other two genes are APP (amyloid protein precursor), accounting for 1-15% of EOFAD and PSEN2 (presenilin 2) accounting for less than 5% of EOFAD.

Since PSEN1 is a dominant gene, it only takes one mutated copy, inherited from either your mother or father, to cause EOFAD. Why PSEN1 mutations are associated with EOFAD is not completely understood. It is thought that the normal role of the PSEN1 gene is to make the protein presenilin 1, a protein used in the development of the brain and spinal cord. It also works with other enzymes to cut certain proteins into smaller pieces (including amyloid beta protein). A mutation of PSEN1 produces an abnormal presenilin 1 protein that no longer functions properly, resulting in a breakdown of this process. This leads to increased production of the longer, stickier configuration of the amyloid beta protein, which is toxic to the nervous system and eventually forms the characteristic amyloid plaques of AD. So far, more than 150 mutations of the PSEN1 gene have been identified, but only in a limited number of families worldwide.

The PSEN1 genetic mutation analysis is relatively new and is only offered by a very limited number of laboratories. The large number of mutations currently known suggests that there may be additional mutations not yet known; thus this test will not identify every person who has a PSEN1 mutation. The analysis is made easier if a patient already has an identified PSEN1 mutation in their families.

How is the sample collected for testing?

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

Is any test preparation needed to ensure the quality of the sample?
No preparation is needed.

The Test

How is it used?

PSEN1 genetic mutation analysis is used to screen symptomatic adults (with dementia-related symptoms) who have a strong family history of early onset familial Alzheimer's disease (EOFAD). This is known as diagnostic testing. Testing may also be performed in asymptomatic adults where a PSEN1 mutation has been identified in other family members, to determine the likelihood of developing early onset dementia (predictive testing). Appropriate professional genetic counselling should be pursued before testing, especially for predictive testing, and when assessing the risk of a patient having and passing on a PSEN1 mutation to his/her offspring. PSEN1 testing is rarely ordered prenatally.

When is it requested?

The test can be used in asymptomatic or symptomatic adults with a strong family history of early onset Alzheimer's disease, for diagnostic or predictive testing as discussed above. It is NOT useful as a screen for the general population or for those who have late onset AD.

What does the test result mean?

If you have one of the PSEN1 mutations, it is highly likely that you will eventually develop EOFAD (i.e. 'penetrance' is close to 100% by age 65), and usually at a similar age to other affected family members. However, the 'expressivity' of the gene mutation (symptoms, severity, and rate of progression), can vary from individual to individual. Since PSEN1 mutations are dominant, if you have a PSEN1 mutation, each of your children will have a 50% chance of inheriting the PSEN1 mutation and developing EOFAD.

If the PSEN1 genetic mutation analysis is negative, it is still possible that the person has EOFAD because the mutation is not identified by the existing testing method. This may be due to a different mutation of the PSEN1 gene or a mutation of another gene (e.g. APP, PSEN2 or another gene yet to be identified).

Is there anything else I should know?

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 and expensive test that has limited use and is still very rarely requested. It is performed in only a few laboratories in the world (including one in Australia), so if your doctor recommends the test, your blood sample will need to be sent to a reference laboratory and results may take a while to return. There is currently no Medicare rebate for PSEN1 testing.

Common Questions

My father has been diagnosed with early onset AD. Can my doctor tell if my father has a genetic mutation without a blood test?

No, the symptoms for EOFAD, 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 them. If there is a strong family history of early onset AD, and especially if another family member has been diagnosed with a genetic mutation, your doctor may suspect a genetic problem, but a blood test is the only way to confirm this suspicion.

What other genes cause EOFAD and is testing available for them?

The other genes that have mutations associated with EOFAD are PSEN2 and APP. Clinical testing for these genes is available in Australia but is not Medicare rebated. It should be noted that PSEN2 and APP mutations are very rare. They have only been identified in a very small number of specific family lines.

Last Review Date: February 15, 2020

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