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Cited by 8Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchLipoproteins and Cardiovascular Health

Estimation of the allelic status of apolipoprotein E4 isoforms with fully automated LUMIPULSE® assays

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Yuri, Tatsushi, Degrieck, Rosina, Minczakiewicz, Dagmara, Sato, Hideo, Kamada, Jo, Nakazawa, Takuya, Vandenbroucke, Ina, Aoyagi, Katsumi +1 more·2023·Exploration of Neuroscience
DOI 10.37349/en.2023.00024
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Abstract

Aim: Apolipoprotein E (ApoE) isoforms, especially the ApoE4 isoform, are genetic risk factors for Alzheimer’s disease (AD). Moreover, the APOE ε4 haplotype has a dose-dependent association with an increased risk of amyloid-related imaging abnormalities (ARIA) in individuals receiving disease-modifying therapy for AD. Therefore, the importance of APOE genotyping or proteotyping has been highlighted. Here, the authors developed fully automated chemiluminescence enzyme-immunoassay kit for ApoE4 and Pan-ApoE, and evaluated their diagnostic concordance with the APOE genotyping. Methods: One hundred seventy-eight specimens were analyzed using the Lumipulse® G ApoE4 and Pan-ApoE for the ApoE proteotype and evaluated its diagnostic concordance with the APOE genotype. Results: The ApoE4 kit specifically detected the ApoE4 concentration in plasma samples, and the polymorphism could be classified clearly by the ratio of ApoE4 and Pan-ApoE amount in plasma. Conclusions: The combination of Pan-ApoE and ApoE4-specific chemiluminescent enzyme immunoassay (CLEIA) assay is useful for predicting APOE ε4 allele status.

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  • Predefined manufacturer thresholds (<5% for absence of ε4, 5-74% for heterozygosity, ≥75% for homozygosity), pre-specified based on previous studies using the same assay platform, effectively stratified patients in this cohort without cohort-specific optimization, aligning with genotyping results.

    “Importantly, predefined manufacturer thresholds (< 5% for absence of ε4, 5–74% for heterozygosity, ≥ 75% for homozygosity), pre-specified based on previous studies using the same assay platform [27], effectively stratified patients in our cohort without the need for cohort-specific optimization, aligning with genotyping results”

    From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [27]

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  • Calibrators and internal quality controls provided by the manufacturer were used according to standard laboratory procedures.

    “Calibrators and internal quality controls provided by the manufacturer were used according to standard laboratory procedures [27, 28].”

    From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [27]

    The ApoE proteotyping section (page unavailable) says samples were tested according to the instructions for use and measurements used a single calibration run. It does not say that manufacturer-provided calibrators or internal quality controls were used. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • The analytical and diagnostic performance of the Lumipulse ApoE4 and PanApoE immunoassays has been previously evaluated in dedicated validation studies.

    “The analytical and diagnostic performance of the Lumipulse ApoE4 and PanApoE immunoassays has been previously evaluated in dedicated validation studies [27].”

    From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [27]

    The Introduction and Results (pages not provided) describe an evaluation of diagnostic concordance between the Lumipulse ApoE4/Pan-ApoE ratio and APOE genotyping in 178 samples. The paper reports assay measurements and ApoE4 specificity, but our copy does not show a dedicated analytical-performance validation of both immunoassays; that part of the claim is unsupported. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Previous studies using similar assay approaches have shown that ApoE isoform levels are primarily driven by ApoE genotype, with limited influence of demographic factors.

    “In addition, previous studies using similar assay approaches have shown that ApoE isoform levels are primarily driven by ApoE genotype, with limited influence of demographic factors [27].”

    From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [27]

    The Results report that ApoE4 concentrations generally increased with the number of APOE ε4 alleles, supporting an association between measured levels and genotype. The Discussion says participant biomedical information was limited and calls for comparisons with other racial groups; it does not establish that demographic factors have limited influence or that genotype is the primary driver relative to them. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Previous evaluations of Lumipulse-based ApoE proteotyping reported high concordance with ApoE genotyping and accurate discrimination between ε4 non-carriers, heterozygotes, and homozygotes using predefined ratio cut-offs.

    “consistent with previous evaluations of Lumipulse-based ApoE proteotyping reporting high concordance with ApoE genotyping and accurate discrimination between ε4 non-carriers, heterozygotes, and homozygotes using predefined ratio cut-offs [27, 29]”

    From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [27]

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Authors
Yuri, T., Degrieck, R., Minczakiewicz, D., Sato, H., Kamada, J., Nakazawa, T., Vandenbroucke, I., Aoyagi, K., & Nojima, H.
Affiliations
  • Fujirebio (Japan) (JP)
  • Fujirebio (Belgium) (BE)
Corresponding author
Nojima, Hisashi
ORCID
Venue
Exploration of Neuroscience
Publisher
Open Exploration Publishing
Published
2023-10-16
Volume
2
Issue
5
Pages
238-244
ISSN
2834-5347 (ISSN-L)
DOI
10.37349/en.2023.00024
OpenAlex
W4387669517
Cited by
8
References
2
Citations by year
2026: 5 · 2025: 2 · 2024: 1
FWCI
1.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Exploration of neuroscience (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
APOE ε4, apolipoprotein E isoforms, APOE genotyping, chemiluminescent enzyme immunoassay, automated immunoassay, Alzheimer's disease, amyloid-related imaging abnormalities, plasma biomarkers

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