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Understanding APOE genotype reporting: What you need to know

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At PreventionGenetics, most of our genetic test reports classify gene variants as pathogenic, likely pathogenic, or variants of uncertain significance (VUS). However, some genes—like APOE—present unique challenges due to their complex associations with multiple conditions and variable clinical implications.

We recognize this complexity and have tailored our APOE reporting standards to provide health care professionals with the most relevant and actionable information based on the clinical context. 

 

Role of APOE genotypes in disease risk, prevention, and treatment 

The APOE gene is involved in both neurological and cardiovascular health due to its role in lipid metabolism and neuronal repair. The E4 allele (also written as ε4) is the strongest known genetic risk factor for late-onset Alzheimer’s disease, influencing amyloid plaque formation and neuroinflammation.1, 2  

The E2 allele is associated with Type III hyperlipoproteinemia, a rare lipid disorder that significantly increases cardiovascular risk due to impaired clearance of remnant lipoproteins.3   

Understanding a patient’s APOE genotype can help guide personalized treatment strategies. The E3 allele represents the reference sequence and is considered functionally neutral. Individuals with the E4 allele may benefit from early lifestyle interventions, cognitive monitoring, and potentially targeted therapies aimed at reducing amyloid burden or neuroinflammation.4 Individuals who are homozygous for the E2 allele may warrant earlier cardiovascular screening and management of lipid levels to prevent atherosclerosis.2 

As research advances, APOE genotyping is increasingly being integrated into precision medicine frameworks to optimize prevention and treatment plans based on genetic risk.1 

These diverse effects underscore the need for context-specific reporting, which is why we tailor APOE results based on the clinical indication. 

 

APOE reporting FAQ: Your questions answered
 
How do I know if APOE was included in my patient’s test? 

To determine if APOE was analyzed in a previously ordered panel: 

  • Check the “Gene(s) Analyzed” section of the test report. If APOE is listed, it was included in the analysis. 
  • For larger panels like PGmax™ panels, PGxome® tests, or PGnome® tests, this section may be omitted due to report size. In such cases, or if you're unsure, contact PreventionGenetics Customer Support: 
    • Live Chat 
    • Email: support@preventiongenetics.com 
    • Phone: (715) 387-0484 

 

How is APOE reported for neurological indications?

When testing is ordered with an indication of dementia, only the following APOE genotypes are reported: 

  • E4/E4 

  • E4/E3 

  • E4/E2 

Panels using this reporting standard:  

 

How is APOE reported for cardiology and metabolic indications? 

For indications related to lipoprotein disorders, particularly Type III hyperlipoproteinemia, the following genotypes are reported: 

  • E2/E2 

  • E2/E3 

  • E2/E4 

Panels using this reporting standard: 

How is APOE reported in custom panels? 

Reporting for custom panels depends on the clinical indication like in our predefined panels: 

  • Dementia: Reports E4/E4, E4/E3, E4/E2 

  • Lipoprotein disorder: Reports E2/E2, E2/E3, E2/E4 

 

How is APOE reported with targeted testing? 

When targeted testing for the APOE gene is ordered, we report the following genotypes:  

  • E2/E2  

  • E2/E3  

  • E2/E4 

  • E3/E3 

  • E4/E3  

  • E4/E4  

This comprehensive reporting provides a full view of an individual's APOE status. 

 

Can I request additional APOE genotypes? 

At this time, PreventionGenetics does not accommodate requests for APOE genotypes outside of the standard reporting criteria. However, raw data can be provided upon request for further analysis. 

 

How can I exclude APOE from a test? 

If you prefer not to include APOE in their genetic testing: 

  • Use the Custom Panel Tool to: 

    • Build a panel from scratch 

    • Modify an existing panel by adding or removing genes 

  • If the tool doesn’t meet your needs, contact your regional account manager or customer support to request a modified gene list. Note: Pricing remains the same as the original panel. 

 

References: 

1. Yamazaki et al. 2019. PubMed ID: 31367008 

2. Narasimhan et al. 2024. PubMed ID: 38898183 

3. Mahley et al. 2000. PubMed ID: 11701639 

4. Zerba et al. 2000. PubMed ID: 11140944