At a glance

Also known as

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

Why get tested?

To detect a rare genetic fault (pathogenetic variant) 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?

Genetic testing may be offered for 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). Genetic testing is also possible for adults with no symptoms if a PSEN1 genetic fault has already been identified in a family member with EOFAD. Prior to testing, appropriate genetic counselling should be provided. The potential benefits, limitations, and possible consequences of genetic testing will be discussed prior to deciding whether to proceed. Genetic counselling is a helpful step in deciding if testing is right for an individual person and for dealing with the result if testing proceeds – this is especially important for people with no current symptoms of Alzheimer’s disease.

Sample required?

A blood sample drawn from a vein in your arm
 

Confused about genetics?

See our Genetics Information page
 

Test preparation needed?
None
 

What is being tested?

This test looks for genetic faults (pathogenetic variants) 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 variant. There have been pathogenetic variants 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 precursor protein ), 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 faulty copy, inherited from either your mother or father, to cause EOFAD. Why genetic variants in PSEN1 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 faulty copy 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. A wide variety of pathogenic PSEN1 variants have been identified in the families studied to date.

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 testing may be performed in 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 offered for asymptomatic adults where a PSEN1 gene fault (pathogenetic variant) 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 variant to his/her offspring. 

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 Alzheimer's disease.

What does the test result mean?

If a person has a genetic fault (pathogenic variant) in the PSEN1 gene,  it is highly likely that the person will eventually develop EOFAD, and usually at a similar age to other affected family members. However the symptoms, severity, and rate of progression, can vary from individual to individual. Since pathgenetic PSEN1 variants are dominant, if someone has a PSEN1 variant, each of their children will have a 50% chance of inheriting the variant and developing EOFAD.

Is there anything else I should know?

Genetic testing of PSEN1 cannot detect 100% of pathogenic variants; thus, even with a negative result there is still a chance that there is a PSEN1 variant present that was not identified by the testing method utilised. A negative PSEN1 result in a person with early onset Alzheimer’s disease may also mean that the person has a variant in a different gene instead (e.g. APP, PSEN2 or another gene yet to be identified).

Pathogenic variants in PSEN1 are almost exclusively family-related. Occasionally, a strong family history of EOFAD may not be apparent e.g. because certain family members passed away before symptoms developed or because there is occurrence of a new variant. Other issues that could confound family history are non-paternity and undisclosed adoption.

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 are known to be 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 genetic faults (pathogenetic variants) in PSEN2 and APP mutations are very rare. 


Last Review Date: September 30, 2020


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