Description
Advanced Genetic Testing for Inherited Early-Onset Alzheimer’s Disease
APP + PSEN1 + PSEN2
When Alzheimer’s disease develops at an unusually young age—particularly when several members of the same family have been affected—genetics can provide important answers.
The Early-Onset Alzheimer’s NGS Diagnostic Test uses advanced Next-Generation Sequencing (NGS) to analyze three of the most important genes known to cause autosomal-dominant early-onset familial Alzheimer’s disease:
APP – Amyloid Precursor Protein PSEN1 – Presenilin 1 PSEN2 – Presenilin 2
Unlike genetic tests that simply estimate susceptibility to Alzheimer’s disease, this test looks for pathogenic genetic variants known to cause inherited forms of early-onset Alzheimer’s disease.
More Than an Alzheimer’s Risk Test
Many people have heard of APOE genetic testing for Alzheimer’s disease. APOE can influence a person's risk of developing Alzheimer’s, but it does not by itself determine whether someone will develop the disease.
Testing APP, PSEN1 and PSEN2 serves a different purpose.
Certain pathogenic variants in these genes can cause autosomal-dominant familial Alzheimer’s disease, a rare inherited form of Alzheimer’s that frequently begins before age 65.
For the right individual or family, identifying one of these variants can provide extremely important information.
The Three Genes Tested
PSEN1 – Presenilin 1
PSEN1 is the most common known genetic cause of autosomal-dominant early-onset Alzheimer’s disease.
Pathogenic PSEN1 variants can cause Alzheimer’s disease at a much younger age than the more common late-onset form.
APP – Amyloid Precursor Protein
The APP gene provides instructions for producing amyloid precursor protein.
Certain pathogenic variants can alter amyloid processing and lead to the accumulation of beta-amyloid associated with familial early-onset Alzheimer’s disease.
PSEN2 – Presenilin 2
PSEN2 pathogenic variants are a less common cause of familial Alzheimer’s disease.
Age of onset and disease expression can be more variable in families carrying PSEN2 variants.
Who May Consider This Test?
This test may be particularly important when there is:
- Alzheimer’s disease or progressive dementia developing before age 65
- Dementia occurring at an unusually young age
- Multiple generations of a family affected by early-onset Alzheimer’s disease
- A parent, sibling or other relative with a known APP, PSEN1 or PSEN2 pathogenic variant
- A clinical suspicion of autosomal-dominant familial Alzheimer’s disease
- A need to help clarify whether early-onset Alzheimer’s disease has an identifiable inherited cause
The test may also be used for presymptomatic genetic testing in appropriate adults from families affected by a known or strongly suspected hereditary form of early-onset Alzheimer’s disease.
Why Can This Information Be So Important for a Family?
Autosomal-dominant inheritance means that when a parent carries a disease-causing variant, each biological child generally has a 50% chance of inheriting that variant.
Identifying a pathogenic variant can therefore provide information not only for the individual being tested but potentially for other biological family members.
Because of the potential implications for the person being tested and their relatives, genetic counseling is strongly recommended, particularly when testing someone who does not currently have symptoms.
What Does NGS Mean?
NGS stands for Next-Generation Sequencing.
This technology allows the laboratory to examine the DNA sequence of multiple genes simultaneously and look for genetic changes associated with disease.
This panel specifically focuses on:
APP • PSEN1 • PSEN2
Understanding Your Results
Pathogenic/Likely Pathogenic Variant
A disease-causing or likely disease-causing genetic variant has been identified. The significance depends on the specific gene, variant, clinical history and family history.
Negative
No reportable pathogenic variant was identified in the genes tested.
A negative result does not rule out Alzheimer’s disease and does not eliminate the possibility of another genetic cause of dementia.
Variant of Uncertain Significance (VUS)
A genetic variant was identified, but current scientific evidence is not sufficient to determine whether it causes disease.
A VUS should generally not be treated the same as a confirmed disease-causing mutation.
Important: This Test Is Not the Same as APOE Testing
APOE testing evaluates genetic susceptibility or risk.
APP, PSEN1 and PSEN2 testing looks for rare pathogenic variants that can directly cause inherited early-onset familial Alzheimer’s disease.
The distinction is important when choosing the appropriate genetic test.
Important Information
Early-onset familial Alzheimer’s disease caused by APP, PSEN1 or PSEN2 variants represents only a small proportion of all Alzheimer’s disease.
Most people with Alzheimer’s disease—even some people who develop symptoms before age 65—will not have a pathogenic variant identified in one of these three genes.
This test is intended for adults and is not appropriate for predictive testing of children.
Results should be interpreted in the context of the individual's symptoms, age of onset, neurological evaluation and family history. Genetic counseling may be particularly valuable before and after predictive testing.
How Do I Get the Test?
The Early-Onset Alzheimer’s NGS Diagnostic Test can be performed using a blood sample.
1. Order the Test
The test must first be ordered so the appropriate testing paperwork and collection requirements can be arranged.
2. Come to Labs By Request for Collection
Once your test is ready for collection, come to Labs By Request for your blood draw.
3. We Collect Your Blood Sample
A small blood sample is collected for DNA analysis.
4. Your DNA Is Analyzed
Next-Generation Sequencing is used to analyze the APP, PSEN1 and PSEN2 genes for reportable genetic variants.
5. Receive Your Genetic Report
Your report provides the genetic findings and their laboratory interpretation.
Typical turnaround time: approximately 14–28 days.
