At a glance
Also known as
PS1; PS-1; AD3; Presenilin 1; S182
Why get tested?
To screen for a rare 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 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.
A blood sample drawn from a vein in your arm
Confused about genetics?
See our Genetics Information page
What is being tested?
This test looks for 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 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 presenilin 1, a protein used in the development of the brain and spinal cord. It also works with other 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.
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 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 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.