{
  "abstract": "Sex and APOE {varepsilon}4 influence dementia risk, but whether its molecular predictors differ across sex and APOE {varepsilon}4 strata remains unclear. We investigated plasma proteomic and metabolomic signatures predicting future dementia in 43,759 UK Biobank participants across four sex-by-APOE {varepsilon}4 groups. The association between APOE {varepsilon}4 carrier status and dementia differed by sex (interaction p = 0.027). Machine-learning models achieved higher discrimination in APOE {varepsilon}4 carriers (AUC 0.85-0.90) than non-carriers (AUC 0.74-0.76), with the highest performance in female carriers. Most top molecular predictors were subgroup-specific, including C7, CDON and EDIL3 in female carriers and KLK4, MMP12 and TGFBI in male carriers. When UK Biobank models were applied to the Global Neurodegeneration Proteomics Consortium, 12/17 available top predictors in female carriers and 10/16 in male carriers remained highly ranked. These findings identify distinct molecular signatures of dementia risk across sex and APOE {varepsilon}4 strata, supporting stratified biomarker discovery.",
  "abstract_shown": true,
  "affiliations": [
    "Centre for Preventive Neurology, Queen Mary University of London, London, United Kingdom"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "S. Calhas"
    },
    {
      "name": "Y. Liu"
    },
    {
      "name": "S. Waters"
    },
    {
      "name": "D. Abdolkarimi"
    },
    {
      "name": "C. Legido-Quigley"
    },
    {
      "name": "O. Blyuss"
    },
    {
      "name": "C. R. Marshall"
    },
    {
      "affs": [
        0
      ],
      "name": "P. Proitsi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/by26x434faeem.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.02.26366836",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.11.02.26366836v1.full",
  "id": "by26x434faeem",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.11.02.26366836v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "neurology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.11.02.26366836v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/by26x434faeem.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T00:21:05Z",
      "native_id": "10.64898/2026.11.02.26366836",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.11.02.26366836v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:neurology",
      "subfield": "neurology"
    }
  ],
  "title": "Sex shapes plasma molecular signatures of dementia risk across APOE ε4 strata",
  "title_text": "Sex shapes plasma molecular signatures of dementia risk across APOE ε4 strata",
  "type": "preprint",
  "updated_at": "2026-11-05T00:20:37Z",
  "url": "https://research.draconitic.com/paper/by26x434faeem",
  "venue": "medRxiv",
  "versions": []
}