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PSEN1

Also known as: PS1; PS-1; Presenilin 1 gene; S182
Formal name: PS1 or PSEN1 genetic mutation analysis
Related tests: ApoE; Tau/Aß42

At a Glance

Why Get Tested?

To screen for a rare mutation in the PSEN1 gene known to be associated with Early Onset Familial Alzheimer's Disease (EOFAD, also called Alzheimer's disease Type 3 or AD3)

When to Get Tested?

When you are an adult who has symptoms of dementia and a strong family history of Alzheimer's Disease that begins before age 60-65 or if you are an asymptomatic adult with an identified PSEN1 genetic mutation and early onset Alzheimer's Disease in your family line

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?

None

The Test Sample

What is being tested?

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.

How is the sample collected for testing?

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

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.

The Test

How is it used?

PSEN1 genetic mutation analysis is used to screen asymptomatic or symptomatic adults who have a strong family history of early onset Alzheimer's Disease (EOFAD, also called Alzheimer's Disease Type 3 or AD3), especially when a PSEN1 mutation has been identified in other family members. It may be used to aid in the differential diagnosis of EOFAD, versus other forms of early onset dementia, but usually only in those with a family history of AD3. Appropriate genetic counseling may be pursued to assess the risk of either parent having and passing on a PSEN1 mutation. PSEN1 is rarely ordered prenatally.

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When is it ordered?

This test may be ordered when a person develops symptoms associated with Alzheimer's Disease before 65 years of age. PSEN1 mutation analysis may also be ordered when an asymptomatic adult has a strong family history of early onset Alzheimer's Disease, especially when there are multiple family members over several generations who have or thought to have had AD3. Because an amniocentesis is required, it is rarely ordered prenatally and only when there is documented affected family members. It is not common practice to test prenatally for adult-onset diseases. This test is NOT useful as a screen for the general population or for those who have late onset AD.

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What does the test result mean?

If a person has one of the PSEN1 mutations, it is highly likely that that he will eventually develop AD3, usually at a similar age to other affected family members. The penetrance of the gene (i.e., the symptoms, the severity, and the rate of progression), can vary from individual to individual. Since it is a dominant gene, each child will have a 50% chance of having the PSEN1 mutation gene passed on to them.

If the PSEN1 genetic mutation analysis is negative, it is still possible that the person has AD3 because the mutation is not identified by the existing testing method. This may be due to a different mutation of the PSEN1 gene or a mutation of another gene yet to be identified.

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Is there anything else I should know?

PSEN1 genetic mutation is almost exclusively family-related and is not associated with late onset AD. A few cases of PSEN1 genetic mutation will show up without a strong family history because of "alternate" paternity, new mutations, or because a parent died before symptoms developed so this element of the family history was unknown.

The PSEN1 test is a new, comparatively expensive test that has limited use and is still rarely ordered. It is performed in only a few laboratories in the world, so if your doctor recommends the test, your blood sample will need to be sent to a reference laboratory and results may take awhile to return. As with many new testing modalities, the analysis may be costly and is often not covered under most insurance plans.

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Common Questions

1.  My father has been diagnosed with early onset Alzheimer's Disease (AD3). Can my doctor tell if my father has a genetic mutation without a blood test?

No, the symptoms for AD3, 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 mutation just by looking at their perceived abnormal daily living activities. If there is a strong family history of early onset AD, especially if another family member has been diagnosed with a genetic mutation, your doctor may suspect a genetic problem that may be confirmed by a blood test.

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2.  Are there any other genetic tests that will diagnose AD?

The other genes that have mutations associated with AD3 are PSEN2 and APP (amyloid precursor protein). PSEN2 testing is available, but APP testing is available only in a couple of places in the world at this time. It should be noted that PSEN2 and APP mutations are very rare and have been identified in a very small number of specific family lines.

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Article Sources

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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Sources Used in Current Review

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Bird, T. (Revised 2009 April 28). Early-Onset Familial Alzheimer Disease. GeneReviews [On-line information]. Available online at http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene∂=alzheimer-early through http://www.ncbi.nlm.nih.gov. Accessed August 2009.

Anderson, H et. al. (Updated 2009 June 18). Alzheimer Disease. emedicine [On-line information]. Available online at http://emedicine.medscape.com/article/1134817-overview through http://emedicine.medscape.com. Accessed August 2009.

Rogaeva, E. (2009 February 5). The Genetic Profile of Alzheimer's Disease: Updates and Considerations. Medscape Today from Geriatrics & Aging [On-line information]. Available online at http://www.medscape.com/viewarticle/586756 through http://www.medscape.com. Accessed August 2009.

Mayo Clinic Staff (2008 September 17). Alzheimer's: Is it in your genes? MayoClinic.com [On-line information]. Available online at http://www.mayoclinic.com/health/alzheimers-genes/AZ00047 through http://www.mayoclinic.com. Accessed August 2009.

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Eastman, P. (2002 March). Keeping Alzheimer's at Bay, Early Diagnosis Keeps Patients Functioning Longer. AARP Bulletin Online [On-line serial]. Available online at http://www.aarp.org/bulletin/departments/2002/health/0310_health_1.html through http://www.aarp.org.

McConnell, S. , et. al. Unraveling the Mysteries of Alzheimer's Disease: Exciting New Developments in Research. From panel sponsored by the Alzheimer's Association [On-line information]. Available online at http://www.asaging.org/am/cia2/alzheimer.html through http://www.asaging.org.

Galasko, D., et. al. (1998). High Cerebrospinal Fluid Tau and Low Amyloid b42 Levels in the Clinical Diagnosis of Alzheimer Disease and Relation to Apolipoprotein E Genotype. Arch Neurol [On-line journal], vol (55) pages (937-945). Available online at http://archneur.ama-assn.org/issues/v55n7/abs/noc7433.html through http://archneur.ama-assn.org.

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