{
  "abstract": "Variants at the CD2AP locus, which encodes a branched-actin regulator, are associated with late-onset Alzheimer's disease (AD), and CD2AP-deficient mice show increased blood-brain barrier (BBB) permeability. CD2AP is enriched in endothelial cells, but its function there is poorly understood. In endothelium, branched actin networks maintain cell-cell junctions and are also required for immune cells to cross through individual endothelial cells (transcellular transendothelial migration, TEM). We previously showed that the Arp2/3 activators N-WASP and WAVE2 contribute to these processes, but the capping protein (CP)-interacting proteins involved are unknown. Here we tested whether CD2AP, a CP-interacting protein recruited to cell-cell contacts, regulates both junction integrity and TEM. In primary human microvascular endothelial cells, shRNA knockdown of CD2AP increased TNF-induced monolayer permeability, measured by transendothelial electrical resistance, and altered VE-cadherin junction morphology. Unexpectedly, on soft hydrogels the same knockdown reduced TEM of NK-92 MI cells, lowering the proportion of transcellular events. Thus, loss of CD2AP weakens the endothelial barrier yet impairs a distinct, actin-dependent route of immune-cell passage. These findings suggest that CD2AP risk variants may affect the BBB through more than permeability, and they identify endothelial immune-cell trafficking as a testable link between CD2AP and AD.",
  "abstract_shown": true,
  "affiliations": [
    "Washington University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "M. D. Onken"
    },
    {
      "name": "J. A. Cooper"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0p8ftabnqgg5y.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.01.755982",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.01.755982v1.full",
  "id": "0p8ftabnqgg5y",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.01.755982v1",
  "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": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "2808|Barrier Structure and Function Studies"
    ]
  ],
  "openalex": "W7215791842",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.01.755982v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0p8ftabnqgg5y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:53Z",
      "native_id": "10.64898/2026.10.01.755982",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.01.755982v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "The Alzheimer's Disease-associated gene CD2AP regulates permeability of endothelial cells and transendothelial migration of immune cells",
  "title_text": "The Alzheimer's Disease-associated gene CD2AP regulates permeability of endothelial cells and transendothelial migration of immune cells",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:58Z",
  "url": "https://research.draconitic.com/paper/0p8ftabnqgg5y",
  "venue": "bioRxiv",
  "versions": []
}