Patient Test Information


  • Why Get Tested?

    To detect a rare mutation in the PSEN1 gene known to be associated with early onset familial Alzheimer disease (EOFAD)

    When To Get Tested?

    When you are an adult who has symptoms of dementia and a strong family history of Alzheimer disease that begins before age 60 to 65 or if you are an asymptomatic adult with a family member who has early onset Alzheimer disease and an identified PSEN1 genetic mutation

    Sample Required?

    A blood sample drawn from a vein

    Test Preparation Needed?

    No test preparation is usually needed. However, prior to testing, you may wish to receive genetic counseling. This could be a helpful and important step in deciding if testing is right for you and for dealing with the result if you decide to be tested – especially if you currently have no symptoms of dementia.

  • 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).

    Although most Alzheimer disease (AD) cases present after the age of 65, about 5-10% of cases present 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 genes that have been identified as being associated with EOFAD: PSEN1, PSEN2, and amyloid precursor protein (APP).

    Of these three genes, PSEN1 is the most commonly involved and is thought to cause about 20% to 70% of early onset AD. Since PSEN1-associated AD is dominantly inherited (autosomal dominant), it only takes one mutated copy, inherited from either the mother or father, to lead to the development of EOFAD.

    Why PSEN1 mutations cause EOFAD is not completely understood. Scientists think 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 peptides). A mutation in PSEN1 produces an abnormal presenilin 1 protein that no longer functions properly, resulting in a breakdown of this process. This can lead 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 in individuals with AD.

    A wide variety of PSEN1 mutations have been identified in the families studied to date, and there is no common or high frequency mutation known. Some mutations may be more common in specific populations. Testing is more straightforward 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 it used?

    PSEN1 genetic mutation analysis may be performed in adults who have a strong family history of early onset Alzheimer disease (EOFAD), especially when a specific 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 strong family history of disease.

    The PSEN1 test is not useful as a screen for the general population or for those who have late onset familial AD or sporadic AD.

    When is it ordered?

    This test may be ordered when you develop symptoms associated with Alzheimer disease before 65 years of age. Signs and symptoms may include:

    • Loss of memory that affects daily life—forgetting information that was recently learned. This can occur with normal aging, but the information is usually remembered later. This includes forgetting important dates or events, having to rely on memory aids, and asking for the same information again and again.
    • Difficulty planning or problem solving, such as keeping track of bills and payments
    • Problems completing usual tasks, such as forgetting how to get to a familiar location
    • Confusion about place or time—losing track of time, forgetting where you are or how you got there
    • Increasing difficulty reading or judging distances
    • Problems speaking or writing—forgetting words, repeating the same thing, struggling with vocabulary
    • Losing things more frequently and not being able to logically retrace steps to find them
    • Impaired judgment, such as giving away unusually large amounts of money
    • Increasing withdrawal from activities, including social, work or family events
    • Changes in mood and personality, such as increasing anxiety, fear, suspicion and depression

    PSEN1 mutation analysis may also be ordered when an asymptomatic adult has a strong family history of early onset Alzheimer disease, especially when there are multiple family members over several generations who have had or were thought to have had EOFAD.

    What does the test result mean?

    If a person has a disease-causing PSEN1 mutation, it is highly likely that the person will eventually develop AD, usually at a similar age to other affected family members. The symptoms, severity, and 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 passed on to them.

    If no PSEN1 mutation is identified, it is still possible that the person has EOFAD because the specific PSEN1 mutation is not able to be identified by the existing testing method or there is a mutation in a different gene.

    Is there anything else I should know?

    PSEN1 mutations are not associated with late onset sporadic AD. Some individuals will not have a strong family history because their family is not informative (i.e., key people passed away before they would have developed symptoms or their full medical histories are not known). Other issues that could confound family history are non-paternity and undisclosed adoption.

    Can this test be done at my local laboratory?

    The PSEN1 test is a relatively new test that has limited use and is still rarely ordered. It is performed in only a few laboratories, so if a healthcare practitioner recommends the test, the blood sample will need to be sent to a reference laboratory.

    My father has been diagnosed with early onset Alzheimer disease. Can my doctor tell if my father has a genetic mutation without a blood test?

    No, the clinical symptoms of all forms of AD are often the same. They only differ by age of onset. You cannot tell whether someone has an inherited form of AD just by looking examining them. If there is a strong family history of early onset AD, especially if another family member has had positive genetic testing, your doctor may suspect a genetic problem that may be confirmed by a blood test.

    Are there any other genetic tests that will diagnose AD?

    The other genes that have mutations associated with EOFAD are PSEN2 and APP (amyloid precursor protein). Testing is available, but these are less frequent causes of EOFAD.

  • View Sources

    Sources Used in Current Review

    Giri, M. et. al. (2016 May 17). Genes associated with Alzheimer's disease: an overview and current status. Clin Interv Aging. 2016 May 17;11: 665-81. Available online at Accessed February 2019.

    (© 2018). Genetics. Alzheimer's association. Available online at Accessed February 2019.

    Huang, J. (2018 March, Revised). Alzheimer Disease. Merck Manual Professional Version. Available online at Accessed February 2019.

    Lanoiselee, H. et. al. (2017 March 28). APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS Med. 2017 Mar 28;14 (3). Available online at Accessed February 2019.

    Kelleher III, R. and Shen, J. (2017 January 24). Presenilin-1 mutations and Alzheimer's disease. PNAS January 24, 2017 114 (4) 629-631. Available online at Accessed February 2019.

    Anderson, P. (2018 February 6). Triple Threat: Alzheimer's Biomarkers Occur in Sequence. Medscape Neurology News. Available online at Accessed February 2019.

    (2013 December, Reviewed). PSEN1 gene. Genetics Home Reference. Available online at Accessed February 2019.

    Punsky, K. (2017 February 28). Mayo Clinic publishes genetic screen for Alzheimer's in African-Americans. Mayo Clinic. Available online at Accessed February 2019.

    Sources Used in Previous Reviews

    Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

    Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

    Sloane, P. (1998, November 1). Advances in the Treatment of Alzheimer's Disease. American Family Physician by the American Academy of Family Physicians [On-line journal]. Available online at

    Eastman, P. (2002 March). Keeping Alzheimer's at Bay, Early Diagnosis Keeps Patients Functioning Longer. AARP Bulletin Online [On-line serial]. Available online at

    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

    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

    ARF (1996-2002). Standard Medical Workup for Alzheimer's Disease. Alzheimer Research Forum [On-line information]. Available online at

    Family Caregiver Alliance. Fact Sheet: Alzheimer's Disease [On-line information]. Available online at

    Bird, T. (2001 June 22 last update). Alzheimer Overview. GeneReviews [On-line information. Note: It is necessary to register to use GeneReviews, but it is a free site, funded by the NIH]. Available online through

    Gottlieb, F. and Lambert, J. G., [Updated by] (2002, January 2, last update). Alzheimer's Disease. MEDLINEplus [On-line information]. Available online at

    Miller, M. (1998 February 18). 26 national Alzheimer's Disease Centers Collaborate on Study of the Utility of Genetic Testing for Alzheimer's. National Institutes of Health News Release [On-line press release]. Available online at

    NIH (2000). Progress report on Alzheimer's disease, taking the next steps. NIH Publication No. 00-4859 [On-line report]. Available online at

    UniSci (2002, April 08). New Approaches Seen For Early Alzheimer's Diagnosis. Daily University Science News [On-line Article]. Review of two studies found in Neuropsychology, Vol 16 (2). Available online at

    Eldercare (2002 February 28, last update). Is it Alzheimer's ... or Just Forgetfulness? Sponsored by Nebraska's Area Agencies on Aging [On-line information]. Available online at

    Diagnostic Education, Neurological Disorders, Alzheimer's Disease. Athena Diagnostics [On-line information]. Available online at

    NeuroCast. Neuropathology of Alzheimer's Disease. Athena Diagnostics [On-line information]. Available online at's.shtml.

    NeuroCast. Biochemistry of Alzheimer's Disease. Athena Diagnostics [On-line information]. Available online at's.shtml.

    Hain, T. (2000 February 13). Alzheimer's Disease. Neurology, Northwestern University Medical School [3rd year neurology medical student curriculum material]. Available online at

    Kleiner-Fisman, G., Updated by (2002 January 2, last update). CSF Collection. MedlinePlus [On-line information]. Available online at

    (Reviewed 2008 December). PSEN1. Genetics Home Reference [On-line information]. Available online at Accessed August 2009.

    Bird, T. (Revised 2009 April 28). Early-Onset Familial Alzheimer Disease. GeneReviews [On-line information]. Available online at∂=alzheimer-early. Accessed August 2009.

    Anderson, H et. al. (Updated 2009 June 18). Alzheimer Disease. emedicine [On-line information]. Available online at 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 Accessed August 2009.

    Mayo Clinic Staff (2008 September 17). Alzheimer's: Is it in your genes? [On-line information]. Available online at Accessed August 2009.

    Grandy, J. (2011 June 16). What's new in Alzheimer disease? Biomarkers and gene mutations as aids for detecting AD early. JAAPA [On-line information]. Available online at Accessed April 2013.

    Bird, T. (Revised 2012 October 18). Early-Onset Familial Alzheimer Disease. NCBI GeneReview [On-line information]. Available online at Accessed March 2014.

    Mayo Clinic Staff (2011 March 31) Early-onset Alzheimer's: When symptoms begin before age 65. Mayo Clinic [On-line information]. Available online at Accessed March 2014.

    Bird, T. (Revised 2014 January 30). Alzheimer Disease Overview. NCBI GeneReview [On-line information]. Available online at Accessed March 2014.

    Mayo Clinic Staff (2013 February 9). Alzheimer's genes: Are you at risk? Mayo Clinic Accessed March 2014.

    Anderson, H. (Updated 2014 March 3). Alzheimer Disease. Medscape Reference [On-line information]. Available online at Accessed March 2014.

    Stetka, B. (2013 April 1). Alzheimer Biomarkers in Clinical Practice. Medscape Today News [On-line information]. Available online at Accessed March 2014.