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Formal name: PS1 or PSEN1 Genetic Mutation Analysis

The Test Sample

What is being tested?

This test looks for mutations in the PSEN1 gene sequence that have been associated with early onset familial Alzheimer disease (EOFAD, also called Alzheimer disease type 3 or AD3).

Although most Alzheimer disease (AD) cases start after the age of 65, about 5-10% of cases begin in people younger than 65 years of age. Much of this early onset AD is familial – it runs in family lines and is caused by a genetic mutation. So far, there have been three rare gene mutations that have been identified as being associated with AD3: PSEN1, PSEN2, and amyloid precursor protein (APP).

PSEN1 is the most common of these gene mutations 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 lead to the development of AD3.

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 presenilin 1, a protein used in the development of the brain and spinal cord. Presenilin 1 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 a longer, stickier configuration of the amyloid beta protein, which is toxic to the nervous system and eventually forms the characteristic amyloid plaques seen with AD.

So far, more than 150 mutations of the PSEN1 gene have been identified in a limited number of different family lines worldwide. The large number of mutations suggests that there may be additional mutations not yet known; thus, the PSEN1 test will not identify every person who has a PSEN1 mutation.

The analysis is made easier if a specific PSEN1 mutation has already been identified in a person's family line. The PSEN1 genetic mutation analysis is a relatively new test and is offered by a limited number of laboratories.

How is the sample collected for testing?





No test preparation is needed.