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journal article·2026-01Open access

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

Paola Sebastiani, Eric Reed, Kevin B Chandler, Prisma Lopez, Hannah Lords, Harold Bae, Catherine E Costello, Matthew Au, Lingyi Lynn Deng, Mengze Li, Qingyan Xiang, Heeju Noh, Lance Pflieger, Cory Funk, Noa Rappaport, Marianne Nygaard, Meghan I Short, Michael Brent, Stefano Monti, Stacy L Andersen, Thomas T Perls

Advanced Science· Volume 13· Issue 4
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Abstract

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.
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Research context

OpenAlex topics: Alzheimer's disease research and treatments · Advanced Proteomics Techniques and Applications · Clusterin in disease pathology

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Affiliations

Institute for Clinical Research and Health Policy Studies Tufts Medical Center Boston MA USA

School of Medicine Tufts University Boston MA USA

Albert Einstein College of Medicine Bronx NY USA

Center for Biomedical Mass Spectrometry Department of Biochemistry and Cell Biology Boston University Chobanian & Avedisian School of Medicine Boston MA USA

Department of Cellular and Molecular Medicine Florida International University Miami FL USA

Division of Computational Biomedicine Department of Medicine Boston University Chobanian & Avedisian School of Medicine Boston MA USA

College of Health Oregon State University Corvallis OR USA

Chobanian & Avedisian School of Medicine Boston University Boston MA USA

Department of Biostatistics Vanderbilt University Medical Center Nashville TN USA

Institute for Systems Biology Seattle WA USA

Phenome Health Seattle WA USA

Buck Institute for Research on Aging Novato CA USA

Epidemiology Biostatistics and Biodemography Department of Public Health University of Southern Denmark DK Odense DK‐5230 Denmark

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