{
  "abstract": "Apolipoprotein E (APOE) genotype is theorised to influence dementia risk partly through effects on blood-brain barrier (BBB) function, but clinical studies examining APOE effects on BBB biomarkers report inconsistent results. Therefore, this systematic review and meta-analysis quantified associations between APOE genotype and two commonly used fluid biomarkers of CNS barrier function: cerebrospinal fluid (CSF)/serum albumin quotient (Q-Alb), and soluble platelet-derived growth factor receptor beta (sPDGFR{beta}). Ovid MEDLINE, Embase, and Web of Science were searched on 30th June, 2026. Eligible peer-reviewed human studies reported Q-Alb or blood or CSF sPDGFR{beta} by APOE genotype. Risk of bias was assessed using the Joanna Briggs Institute checklist. Twenty-eight studies involving 5,375 participants were included: 17 assessed Q-Alb and 11 assessed sPDGFR{beta}. Random-effects meta-analyses determined that APOE {varepsilon}2 carriage was associated with higher Q-Alb (g = 0.29, 95% CI 0.11 to 0.46). APOE {varepsilon}4 carriage was not associated with Q-Alb overall (g = .13, 95% CI -.17 to .43) or sPDGFR{beta} overall (g = .10, 95% CI -.21 to .40). Genotype-specific Q-Alb analyses suggested medium positive but non-significant effects among {varepsilon}4/{varepsilon}4 and {varepsilon}2/{varepsilon}4 carrier subgroups. For sPDGFR{beta}, exploratory subgroup analysis revealed effect estimates near zero in cognitively unimpaired participants, and a small positive non-significant effect in cognitively impaired participants. Larger effects were also observed in samples with an older mean age, although this was not statistically significant. Overall, evidence for APOE {varepsilon}4-associated alterations in Q-Alb and sPDGFR{beta} remained inconclusive, highlighting the need for further study across the spectrum of cognitive ageing and dementia. In contrast, APOE {varepsilon}2 carriage was associated with greater barrier dysfunction as indexed by Q-Alb, broadening the predominant focus on APOE {varepsilon}4 and identifying {varepsilon}2 as a potentially important but understudied contributor to altered neurovascular function.",
  "abstract_shown": true,
  "affiliations": [
    "La Trobe University"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "W. Lucas"
    },
    {
      "name": "M. J. Murphy"
    },
    {
      "affs": [
        0
      ],
      "name": "N. Riddell"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7w0gwd2yj1qbe.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.27.26364123",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.27.26364123v1.full",
  "id": "7w0gwd2yj1qbe",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.27.26364123v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "genetic and genomic medicine"
    ],
    [
      "openalex",
      "2808|Barrier Structure and Function Studies"
    ]
  ],
  "openalex": "W7214722143",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.27.26364123v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7w0gwd2yj1qbe.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "10.64898/2026.09.27.26364123",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.27.26364123v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:genetic and genomic medicine",
      "subfield": "human-genetics"
    }
  ],
  "title": "APOE Genotype and Fluid Biomarkers of Blood-Brain Barrier Integrity: A Systematic Review and Meta-Analysis",
  "title_text": "APOE Genotype and Fluid Biomarkers of Blood-Brain Barrier Integrity: A Systematic Review and Meta-Analysis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/7w0gwd2yj1qbe",
  "venue": "medRxiv",
  "versions": []
}