English
Background
Apolipoprotein E (APOE) mediates transport of cholesterol and other fats throughout the bloodstream. There are three main APOE isoforms: alleles APOE ε2, APOE ε3, and APOE ε4. The APOE isoforms differ slightly in their amino acid sequences, leading to differences in their functionality and association with pathology for diseases such as Alzheimer's disease. While APOE ε2 may have a protective. effect for Alzheimer’s disease and APOE ε3 is neutral, APOE ε4 is most strongly associated with an increased risk of developing Alzheimer's disease.
Individuals who are homozygous for APOE ε4 (+/+) have a higher risk than APOE ε4 (+/-) heterozygotes, and both APOE ε4 +/+ and APOE ε4 +/- individuals are at a higher risk of developing amyloid-related imaging abnormalities (ARIA) following treatment with lecanemab and donanemab, treatments targeted against amyloid beta in Alzheimer's disease, than individuals not carrying an APOE ε4 allele. The anticipated increase in Alzheimer’s disease cases necessitates a rapid, high-throughput assay to determine APOE ε4 zygosity.
In this study, scientists determined the sensitivity, imprecision, and concordance with PCR of a new APOE ε4 zygosity RUO assay on the Beckman Coulter DxI 9000 and Access 2 Immunoassay Analyzers.
The study found:
- 99.3% concordance with PCR and high correlation with a commercially available APOE ε4 RUO immunoassay
- Time-to-first result of ~20 minutes, with up to 450 tests/hour on the DxI 9000 analyzer
- Time-to-first result of ~25 minutes, with up to 100 tests/hour on the Access 2 analyzer
- Low interference and cross-reactivity with common analytes in neurodegenerative conditions
The concordance data show that the Beckman Coulter APOE ε4 RUO assay may have promise as a foundational blood-based biomarker in research laboratories around the world.
