Doctors use the PSEN2 genetic test to look for an inherited cause when a younger adult develops Alzheimer-type memory loss. A positive result confirms early-onset familial Alzheimer disease and guides family counseling and trial options. PSEN2 is a gene on chromosome 1. It is one of three deterministic genes, with APP and PSEN1, that cause early-onset familial Alzheimer disease with symptoms often before age 65, according to the Alzheimer Society of Canada genetics page.
Medical information disclaimer: This article is for general educational purposes only and does not provide medical advice, diagnosis, or treatment. Always consult a physician or other qualified health professional about symptoms, medications, tests, or treatment decisions.
Table of Contents
- Who is offered this test?
- What does the test involve?
- What does a positive result change?
- What are the limits and next steps?
Who is offered this test?
Doctors usually consider testing when memory decline starts unusually early. Penn Medicine recommends testing for Alzheimer patients with onset under age 60 or with three or more affected relatives in total, according to the Penn Medicine genomic medicine page.
The doctor first rules out other causes of memory problems. These include medication effects, depression, sleep disorders, thyroid disease, and other neurologic conditions. Genetic testing follows when the pattern still points toward familial early-onset disease.
What does the test involve?
The test sequences PSEN2, usually along with APP and PSEN1. Studies of early-onset Alzheimer groups report a 5-13 percent diagnostic yield when the three genes are sequenced together, according to the Penn Medicine genomic medicine page.
A blood or saliva sample is enough for the laboratory. Results may show a disease-causing mutation, a variant of uncertain meaning, or no mutation. A genetics clinician explains what each result can and cannot prove.
What does a positive result change?
A positive PSEN2 result confirms familial early-onset disease. It also lets doctors counsel relatives about 50 percent inheritance risk, family planning, and research or treatment-trial eligibility, according to the BrightFocus Foundation testing resource.
Inheritance is autosomal dominant, so each child of a carrier has a one-in-two chance of carrying the mutation. Lifetime penetrance is about 95 percent, so a minority of carriers never develop dementia. Reported onset for carriers spans roughly ages 40-75, wider and later on average than PSEN1 or APP.
What are the limits and next steps?
Testing an at-risk person cannot predict onset age, symptom type, severity, or progression. Guidelines therefore require pre- and post-test counseling and testing an affected relative first when possible, according to the joint genetics guideline in PMC. Practical steps help families use the result well:.
- Bring a full family history, with ages at first symptoms for affected relatives.
- Ask whether an affected parent or sibling can be tested first.
- Meet with a genetic counselor before and after testing.
- Discuss work, insurance, family planning, and trial referrals before results arrive.
