PSEN1

This test looks for mutations in the PSEN1 gene sequence that has been associated with Early Onset Familial Alzheimer's Disease (EOFAD, also called Alzheimer's Disease Type 3 or AD3). Although most Alzheimer's Disease (AD) cases start after the age of 65 and above, about 5-10% of cases begin in people under 65 years of age. Much of this early onset AD is familial - it runs in family lines and is caused by a genetic mutation. There have been three gene mutations identified so far that are associated with AD3; all are very rare. Of these, PSEN1 is the most common and is thought to cause about 30% to 70% of the cases of AD3. Since PSEN1 is a dominant gene (autosomal dominant), it only takes one mutated copy, inherited from either the mother or father, to cause AD3.

So far, more than 150 mutations of the PSEN1 gene have been identified in a limited number of different family lines worldwide. Why PSEN1 mutations are associated with AD3 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 (amyloid beta peptide). A mutation of PSEN1 produces an abnormal presenilin 1 protein that no longer functions properly, resulting in a breakdown of this process. This breakdown lends itself 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.

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

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

No test preparation is needed.