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 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.
A blood sample drawn from a vein in your arm
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See our Genetics Information page
Test preparation needed?
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 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 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 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.
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 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.