Evaluation of two plasma‐based proteotyping assays against APOE ε4 genotyping in a memory clinic setting: The Gothenburg H70 Clinical Studies
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INTRODUCTION: Apolipoprotein E ( APOE ) ε4 allele status is associated with an increased risk of Alzheimer's disease and should be determined prior to initiation of anti‐amyloid beta antibody treatment, because of increased risk of treatment‐related side effects. Plasma‐based apoE4 proteotyping may be an alternative to genotyping, with limited clinical evidence. METHODS: apoE4 proteotyping was performed on 164 memory‐clinic patients, using one chemiluminescent enzyme immunoassay (CLEIA) and one nucleic acid–linked immunosandwich assay (NULISA). The assays were evaluated against APOE ε4 blood genotyping. RESULTS: The CLEIA had a 100% sensitivity and 98.5% specificity to classify APOE ε4 homozygosity and carriership in relation to genotyping. The NULISA had a 92.9% sensitivity and 97.1% specificity to classify homozygosity and a 100% sensitivity and 98.5% specificity to classify carriership. DISCUSSION: The high performance suggests that the assays may be used as an easily available tool for identifying individuals for definitive APOE ε4 genotyping in a two‐step approach. Highlights: Plasma‐based proteotyping presented good to excellent sensitivity in identifying apolipoprotein E ( APOE ) ε4 homozygosity. The negative predictive value was also very good to excellent, allowing us to rule out APOE ε4 homozygosity with high precision. Assays with excellent precision show potential for identifying individuals for definitive APOE ε4 genotyping in a two‐step approach.
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In line with previous proposals of a stepwise approach, such a model may balance analytical performance with clinical safety while facilitating timely ε4 stratification in the era of anti-amyloid therapies.
“In line with previous proposals of a stepwise approach [36, 37], such a model may balance analytical performance with clinical safety while facilitating timely ε4 stratification in the era of anti-amyloid therapies.”
From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [36]
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Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era
Coraglia, F., Cecchetti, G., Rugarli, G., Spinelli, E. G., Ghirelli, A., Pisano, S., Canu, E., Filippi, M., & Agosta, F. (2026) · Alzheimer's Research & Therapy · doi:10.1186/s13195-026-02089-2 · Cited by 1 · see citing works
- Authors
- Dittrich, A., Blennow, K., Tan, K., Benedet, A. L., Skoog, I., Höglund, K., Ashton, N. J., Zetterberg, H., & Kern, S.
- Affiliations
- Sahlgrenska University Hospital (SE)
- University of Science and Technology of China (CN)
- University of Gothenburg (SE)
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg Gothenburg Sweden
- University of Arizona (US)
- University of Wisconsin System (US)
- Corresponding author
- Dittrich, Anna
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2025-02
- Volume
- 21
- Issue
- 2
- Pages
- e14610-e14610
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC11847986
- OpenAlex
- W4407908145
- Cited by
- 18
- References
- 3
- Citations by year
- 2026: 16 · 2025: 2
- FWCI
- 10.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Hjärnfonden (#FO2017‐0243, #ALZ2022‐0006, FO2024‐0097)
- Alzheimer's Association (SG‐23‐1038904 QC)
- Stiftelsen för Gamla Tjänarinnor
- Vetenskapsrådet (#2023‐00356, 2019‐02075, 2015‐02830, 2013‐8717, 2017‐00639, 2019‐01096, 2022‐00882, #2022‐01018, #2019‐02397, 2019‐02075_15)
- Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse (FO2014‐0207, FO2016‐0214, FO2018‐0214, FO2019‐0163, FO2020‐0235, FO2024‐0341‐HK‐76)
- Alzheimerfonden (AF‐554461, AF‐647651, AF‐743701, AF‐844671, AF‐930868, AF‐940139, AF‐968441, AF‐980935)
- European Partnership on Metrology
- Cure Alzheimer's Fund
- UK Dementia Research Institute (UKDRI‐1003, ALFGBG‐1005471, ALFGBG‐965923, ALFGBG‐81392, ALF GBG‐771071, AF‐842471, AF‐737641, AF‐929959, AF‐939825)
- Stiftelsen Psykiatriska Forskningsfonden
- UCLH Biomedical Research Centre
- H2020 Marie Skłodowska-Curie Actions (860197)
- Familjen Erling-Perssons Stiftelse
- Olav Thon Stiftelsen
- Alzheimer's Drug Discovery Foundation (201809‐2016862)
- Forskningsrådet om Hälsa, Arbetsliv och Välfärd (2013‐1202, 2018‐00471, AGECAP 2013‐2300, 2013‐2496)
- Kirsten og Freddy Johansens Fond
- 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
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Genotype, Homozygote, Humans, Male, Middle Aged, Sensitivity and Specificity, Apolipoprotein E4, Genotyping Techniques
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