Fully automated ApoE4 assay in plasma and the estimation of the APOE polymorphism

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Abstract Background Apolipoprotein E (ApoE) is a major cholesterol carrier that supports lipid transport and injury repair in the brain. APOE polymorphic alleles are the main genetic determinants of Alzheimer disease (AD) risk: individuals carrying the ε4 allele are at increased risk of AD compared with those carrying the more common ε3 allele, whereas the ε2 allele decreases risk. Moreover, it has been reported that the APOE4 haplotype has a dose‐dependent association with an increased risk of amyloid‐related imaging abnormalities (ARIA) in individuals receiving disease‐modifying therapy (DMT) for AD. Therefore, the importance of APOE genotyping or phenotyping and its expanding clinical role in dementia field has been highlighted. Here, we developed fully automated chemiluminescence enzyme‐immunoassay (CLEIA) kits for ApoE4 and pan‐ApoE, and evaluated its diagnostic concordance with the APOE genotyping. Method ApoE4 and pan‐ApoE assays for fully automated platform, LUMIPULSE, are a two‐step sandwich CLEIA with a specific treatment process to extract the antigen from the lipid surface in plasma samples during the 1st immunoreaction. The turnaround time for each reaction is within 30 minutes. Healthy volunteers’ samples were used for the measurement of ApoE4 and pan‐ApoE with CLEIA or the PCR‐Restriction fragment length polymorphism (PCR‐RFLP) analysis for the APOE polymorphism. The study design was approved by the ethics committee at H.U. Group Holdings, Inc in the 2022 fiscal year (22‐012‐01). Result The ApoE4 kit specifically detected the ApoE4 concentration in plasma samples, and could distinguish ApoE polymorphism. Moreover, the polymorphism could be classified clearly by the ratio of ApoE4 and Pan‐ApoE amount in plasma. Conclusion The new CLEIA ApoE4 and pan‐ApoE assay robustly distinguishes among APOE4 carrier status in plasma. Assessing ApoE isoform by CLEIA may help not only clarify ApoE metabolism, but also ARIA risk.

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