Summary

• PSEN1 testing is used to find out if someone has a genetic mutation (also called a variant) that can cause a rare, inherited form of Alzheimer’s disease which occurs in younger people.
• This is early onset familial Alzheimer’s disease (EOFAD).
• PSEN1 testing is mainly used when someone has Alzheimer’s symptoms at a younger age, and/or there is a strong family history of early dementia.
• If a mutation is found, this strongly suggests the person has EOFAD and other family members can choose to be tested.
• Genetic counselling is essential before and after testing.
• If no mutation is found, PSEN1-related Alzheimer's is unlikely, but this does not rule out other types of Alzheimer’s.
• PSEN1 testing is not useful for general population screening or diagnosing late onset Alzheimer’s. There is no Medicare rebate, but the testing may be paid for by a public genetic testing service if you meet their criteria. Otherwise, the test must be paid for privately.

Why get tested?

Early-onset familial Alzheimer’s disease (EOFAD) is a rare, inherited form of Alzheimer’s that causes symptoms like memory loss much earlier than usual, often before age 65. It is caused by specific gene mutations (also called variants) passed down in families. There have been variants identified in three genes that are associated with EOFAD, all of them are rare.

Of these, PSEN1 is the most common and thought to account for up to 70 per cent of EOFAD cases. The other two genes are APP – amyloid precursor protein, accounting for about 15 per cent of EOFAD - and PSEN2 – presenilin 2, accounting for less than five per cent of EOFAD.
More than 300 genetic variants in PSEN1 are linked to EOFAD.

It is thought that the normal role of the PSEN1 gene is to provide instructions 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 the PSEN1 gene produces an abnormal presenilin 1 protein that no longer functions properly, resulting in a breakdown of this process. This leads 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 of Alzheimer's disease.

There are two types of testing:

• Diagnostic testing: PSEN1 genetic testing is ordered for someone who has dementia-related symptoms and a strong family history EOFAD.
• Predictive testing: Testing is also used when have someone does not have symptoms but a PSEN1 gene fault has been identified in other family members. This is to assess the likelihood of them developing EOFAD.

Inheritance
EOFAD is inherited in an autosomal dominant way, meaning a child only needs to inherit one faulty gene from one parent to be at risk of developing EOFAD. This means, any child born from a parent who has the PSEN1 gene fault, has a 1 in 2 chance of inheriting the mutation and a 1 in 2 chance of not inheriting it.

Variants in PSEN1 are almost exclusively family related. However, there can also be what is called a de novo variant in the PSEN1 gene. This refers to a genetic alteration that appears for the first time in a family and develops for the first time in that person.

A de novo genetic alteration can occur when the mother’s egg or father’s sperm is being made or shortly after conception as the embryo begins to develop. A de novo variant in the PSEN1 gene is rare.

Occasionally, a strong family history of EOFAD may not be apparent because family members have passed away before symptoms developed. Other issues that can confound family history are non-paternity and undisclosed adoption.

Genetic counselling
It is important to have professional genetic counselling before deciding on whether to go ahead with testing. This is especially important if you are having predictive testing, to assess the risk of you having a PSEN1 variant and passing it on to your children. Genetic counselling is a helpful step in deciding if testing is the right course of action and for dealing with the result.

Having the test

Sample 
Blood.

Any preparation?
None.

Your results

A positive result means that there is a genetic variant in the PSEN1 gene, it is highly likely a person will eventually develop EOFAD, and usually at a similar age to other family members. However, the symptoms, severity and rate of progression, can vary from person to person.

A negative result means PSEN1-related Alzheimer is unlikely. However, someone with symptoms of EOFAD may have a variant in a different gene such as APP, PSEN2 or another gene yet to be identified. Genetic testing of PSEN1 cannot detect all disease-causing variants, so 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.

There is no Medicare rebate for PSEN1 testing. Similarly, testing for PSEN2 and APP, the other genes known to be associated with EOFAD, although available in Australia, are also not covered by Medicare. If you have testing through a public genetic service, they may pay for the genetic test. It should be noted that genetic faults in PSEN2 and APP are very rare.

Questions to ask your doctor

The choice of tests your doctor makes will be based on your medical history and symptoms. It is important that you tell them everything you think might help.

You play a central role in making sure your test results are accurate. Do everything you can to make sure the information you provide is correct and follow instructions closely.

Talk to your doctor about any medications you are taking. Find out if you need to fast or stop any particular foods or supplements. These may affect your results. Ask:

• Why does this test need to be done?
• Do I need to prepare (such as fast or avoid medications) for the sample collection?
• Will an abnormal result mean I need further tests?
• How could it change the course of my care?
• What will happen next, after the test?

More information

Pathology and diagnostic imaging reports can be added to your My Health Record. You and your healthcare provider can now access your results whenever and wherever needed.

Get further trustworthy health information and advice from healthdirect.