A Robust Serum Proteomic Signature of the E2 Allele of Apolipoprotein E
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.
Authors
- Paola Sebastiani (ORCID: https://orcid.org/0000-0001-6419-1545)
- Kevin Brown Chandler (ORCID: https://orcid.org/0000-0001-5514-9652)
- Michael Richard Brent (ORCID: https://orcid.org/0000-0002-8689-0299)
- Hannah Lords
- Lih‐Wen Deng (ORCID: https://orcid.org/0000-0002-4985-7844)
- Thomas T. Perls (ORCID: https://orcid.org/0000-0002-2492-4334)
- Heeju Noh (ORCID: https://orcid.org/0000-0002-9299-4852)
- Marianne Nygaard (ORCID: https://orcid.org/0000-0003-0703-2665)
- Noa Rappaport (ORCID: https://orcid.org/0000-0001-8643-2055)
- Lance Pflieger (ORCID: https://orcid.org/0000-0003-2237-5674)
- Meghan I. Short (ORCID: https://orcid.org/0000-0002-7849-0180)
- Stefano Monti (ORCID: https://orcid.org/0000-0002-9376-0660)
- Eric Reed (ORCID: https://orcid.org/0000-0003-2347-720X)
- Cory C. Funk (ORCID: https://orcid.org/0000-0002-5229-9011)
- Qingyan Xiang (ORCID: https://orcid.org/0000-0003-4717-3809)
- Mengze Li (ORCID: https://orcid.org/0000-0002-5441-9021)
- Prisma Lopez
- Stacy L. Andersen (ORCID: https://orcid.org/0000-0002-2442-6386)
- Harold Bae (ORCID: https://orcid.org/0000-0003-2219-3969)
- Catherine E Costello (ORCID: https://orcid.org/0000-0001-7158-2675)
- Matthew Au
Institutions
- Boston University (US)
- Tufts University (US)
- Tufts Medical Center (US)
- Albert Einstein College of Medicine (US)
- Oregon State University (US)
- Buck Institute for Research on Aging (US)
- University of Southern Denmark (DK)
- Florida International University (US)
- Institute for Systems Biology (US)
- ProNAi Therapeutics (United States) (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-11-29
- DOI
- https://doi.org/10.1002/advs.202509764
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health
- National Institute on Aging