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. 2026 Jan;13(4):e09764.
doi: 10.1002/advs.202509764. Epub 2025 Nov 29.

A Robust Serum Proteomic Signature of the E2 Allele of Apolipoprotein E

Paola Sebastiani  1   2 , Eric Reed  3 , Kevin B Chandler  4   5 , Prisma Lopez  1 , Hannah Lords  6 , Harold Bae  7 , Catherine E Costello  4 , Matthew Au  8 , Lingyi Lynn Deng  8 , Mengze Li  6 , Qingyan Xiang  9 , Heeju Noh  10 , Lance Pflieger  10   11 , Cory Funk  10 , Noa Rappaport  10   12 , Marianne Nygaard  13 , Meghan I Short  1   2 , Michael Brent  13 , Stefano Monti  6 , Stacy L Andersen  8 , Thomas T Perls  8
Affiliations

A Robust Serum Proteomic Signature of the E2 Allele of Apolipoprotein E

Paola Sebastiani et al. Adv Sci (Weinh). 2026 Jan.

Abstract

A signature of 16 serum proteins that were previously profiled using the aptamer-based Somascan technology highlighted the roles of the e2 allele of APOE in lipid regulation via apolipoprotein B (APOB) and apolipoprotein E (APOE) and in inflammation. Here, the serum protein signature of APOE is validated and expanded using a combination of mass-spectrometry, ELISA, Luminex, blood transcriptomics, and antibody-based Olink serum proteomics. Some of the findings were replicated in the UK Biobank using antibody-based Olink serum proteomics. This analysis replicated the association between APOB and the e2 allele of APOE, detected a new, robust pattern of association between APOE genotypes and the serum level of APOE, and discovered new associations between APOE genotypes and the complex of apolipoproteins APOC1, APOC2, APOC3, APOC4, APOE, APOF, and APOL1. In addition, 13 new proteins correlated with APOE genotypes. This extended signature includes granule proteins CAMP, CTSG, DEFA3, and MPO secreted from neutrophils and points to olfactomedin 4 (OLFM4) as a new target for the prevention of Alzheimer's disease.

Keywords: APOE; aptameter‐based proteomics; gene expression; genetic variants; mass‐spectrometry; omics‐signatures.

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