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Rapid Apolipoprotein E ε4 Proteotyping for Alzheimer's Disease Anti-Amyloid Therapy Eligibility and Risk Assessment
Alkhodair Y, Smith RJY, Helbling C, DeMarco ML.. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 2026-11-09
Topic: Amyloid, tau and blood-test diagnosis
Background Anti-amyloid therapies for Alzheimer's disease (AD) are associated with amyloid-related imaging abnormalities (ARIA), with apolipoprotein E ε4 ( APOE4 ) homozygosity conferring the highest risk. Given the new clinical need, novel plasma proteotyping assays may offer a rapid and high-throughput alternative to existing methods. Methods We evaluated proteotyping performance against real-time polymerase chain reaction (PCR) genotyping in a cohort of 104 participants. Plasma samples were analyzed using apoE4 and total apoE assays on the Fujirebio Lumipulse G1200. APOE4 allelic status (non-carrier, heterozygote or homozygote) was determined from the apoE4-to-total apoE ratio. Analytical validation assessed precision, matrix interference and freeze/thaw stability. Results Proteotyping correctly identified all non-carriers ( n = 53) and all E4/E4 homozygotes ( n = 6). Among 45 heterozygotes, 4 were misclassified as homozygotes, yielding 40% misclassification rate for homozygosity but 100% negative predictive value (NPV). Overall accuracy was 96.2%. The assay performed robustly in the presence of hemolysate and lipemia, with consistent results up to 4 freeze/thaw cycles. Conclusion Proteotyping reliably rules out E4/E4 homozygosity (100% NPV), enabling rapid eligibility screening for anti-amyloid therapies. Positive homozygosity results require confirmatory testing due to the potential for error. Among non-homozygous results, the assay discriminates E4 carriers from non-carriers, supporting ARIA risk stratification. As plasma phospho-tau217 testing is more commonly used, the ability to run plasma apoE4 testing on the same automated clinical immunoassay analyzer (and the same sample) enables a reflexive testing workflow, supporting more efficient treatment decision-making in the era of disease-modifying therapies.
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APA 7th
Alkhodair, Y., Smith, R. J. Y., Helbling, C., & DeMarco, M. L. (2026). Rapid Apolipoprotein E ε4 Proteotyping for Alzheimer's Disease Anti-Amyloid Therapy Eligibility and Risk Assessment. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. https://doi.org/10.1017/cjn.2026.10688
Vancouver
Alkhodair Y, Smith RJY, Helbling C, DeMarco ML. Rapid Apolipoprotein E ε4 Proteotyping for Alzheimer's Disease Anti-Amyloid Therapy Eligibility and Risk Assessment. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. 2026. doi:10.1017/cjn.2026.10688. PMID: 43000884.
BibTeX
@article{alkhodair2026-43000884,
author = {Alkhodair, Y. and Smith, R. J. Y. and Helbling, C. and DeMarco, M. L.},
title = {{Rapid Apolipoprotein E ε4 Proteotyping for Alzheimer's Disease Anti-Amyloid Therapy Eligibility and Risk Assessment}},
journal = {The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques},
year = {2026},
doi = {10.1017/cjn.2026.10688},
pmid = {43000884},
url = {https://doi.org/10.1017/cjn.2026.10688}
}
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Key findings
- Background Anti-amyloid therapies for Alzheimer's disease (AD) are associated with amyloid-related imaging abnormalities (ARIA), with apolipoprotein E ε4 ( APOE4 ) homozygosity conferring the highest risk.
- Results Proteotyping correctly identified all non-carriers ( n = 53) and all E4/E4 homozygotes ( n = 6).
- The assay performed robustly in the presence of hemolysate and lipemia, with consistent results up to 4 freeze/thaw cycles.
- Positive homozygosity results require confirmatory testing due to the potential for error.
- Among non-homozygous results, the assay discriminates E4 carriers from non-carriers, supporting ARIA risk stratification.
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Study details
- Participants53
- Effect size96.2%
- Evidence strengthModerate
How this study scored 57/100
Published in a peer-reviewed journal. Scored zero for study design and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 33 of the 58 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 1 / 4 | 53 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 43000884) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 33 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 33 of the 58 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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