A PSEN2 genetic test measures disease-causing sequence and copy-number changes in the PSEN2 gene. It misses other genetic and non-genetic causes of dementia. PSEN2 is a gene that carries instructions for presenilin-2, a protein piece that helps cut amyloid precursor protein. Harmful changes in this gene can raise toxic amyloid-beta plaque formation linked to Alzheimer disease.
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
- What the sample is checked for
- When doctors order it as symptoms progress
- Why a negative result does not clear the family
- What the test cannot tell you
- What a positive result means for children and planning
What the sample is checked for
The test usually uses next-generation sequencing, a method that reads many DNA pieces at once. It often runs as part of an early-onset dementia panel covering genes including APP, PSEN1 and PSEN2, according to the Mayo Clinic Laboratories test catalog.
PSEN2 encodes presenilin-2, a subunit of the gamma-secretase complex. That complex cuts amyloid precursor protein, and pathogenic variants increase toxic plaque formation, according to the NCBI Gene PSEN2 record.
When doctors order it as symptoms progress
Doctors order the test to confirm suspected familial early-onset Alzheimer disease in a person with symptoms. They also use it to assess at-risk relatives when a family variant is known or when an affected relative cannot be tested.
Testing usually pairs with pre- and post-test genetic counseling. Counseling helps families weigh consent, results, and next steps before blood or saliva is collected.
- Progressive dementia starting at or before age 65
- Family pattern suggesting autosomal-dominant inheritance
- Known PSEN2 variant in a close relative
- Need to clarify trial eligibility, care plans, or family risk
Why a negative result does not clear the family
A negative PSEN2 result does not exclude genetic dementia. Alzheimer dementia can involve APP, PSEN1, APOE and undiscovered variants, and false negatives occur.
Testing identifies a mutation in only about 40%-80% of early-onset cases, according to the Continuum review of genetic testing for early-onset Alzheimer disease. A family with strong early-onset history may still need broader panel testing, repeat review, and neurology follow-up.
What the test cannot tell you
PSEN2 testing does not measure late-onset APOE risk. It cannot by itself diagnose dementia or predict the exact age symptoms will start.
It should not be used for general-population screening without clinical evaluation. Diagnosis still needs exams, cognitive testing, imaging, and exclusion of other causes.
What a positive result means for children and planning
Pathogenic PSEN2 variants cause early-onset autosomal-dominant Alzheimer disease type 4. This rare deterministic form accounts for a small fraction of all Alzheimer cases.
Penetrance is about 95% over a lifetime, with onset commonly reported from 40 to 75 years and up to 40 to 85 years in families. Each child of a carrier has about a 50% chance of inheriting the variant, so families need neurology and genetics follow-up for care, planning, trial options, and support.
