{
  "abstract": "Background: The blood-brain barrier (BBB) is increasingly recognized as an active immunoregulatory interface that responds dynamically to systemic inflammation. As intestinal inflammation can influence brain homeostasis through the gut-brain axis, the endogenous mechanisms that preserve BBB integrity during gut-derived inflammatory stress remain poorly understood. Methods and Results: We combined dextran sulfate sodium-induced colitis, fecal microbiota transplantation, aged mice, APP/PS1 mice, human Alzheimer's disease (AD) brain tissue, single-cell RNA sequencing, in vivo BBB permeability assays, and gain- and loss-of-function approaches to investigate adaptive neurovascular responses to gut inflammation and their mechanism in maintaining BBB integrity. Intestinal inflammation induced a region-specific adaptive response characterized by increased hippocampal vascular remodeling and partial restoration of BBB integrity following the initial inflammatory insult. Single-cell transcriptomic analysis identified a transthyretin (TTR)-enriched vascular-associated microglial state accompanying these neurovascular changes. Functional studies demonstrated that TTR contributes to maintaining BBB integrity by promoting endothelial homeostasis and limiting endothelial endocytosis, consistent with modulation of FcRn-associated transport pathways. This adaptive neurovascular response was progressively attenuated in aged mice and APP/PS1 mice and was accompanied by reduced vascular TTR expression in human AD brains. Conclusion: These findings identify TTR as a contributor of adaptive neurovascular homeostasis during gut-derived neuroinflammation. Impairment of this homeostatic response with aging and AD may contribute to persistent BBB dysfunction and chronic neuroinflammation, highlighting neurovascular resilience as a potential therapeutic target.",
  "abstract_shown": true,
  "affiliations": [
    "Zhejiang University School of Medicine First Affiliated Hospital"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "Z. Xu"
    },
    {
      "name": "J. Chen"
    },
    {
      "name": "J. Yu"
    },
    {
      "name": "J. Duan"
    },
    {
      "name": "Y. Xie"
    },
    {
      "name": "Y. Gong"
    },
    {
      "name": "P. Wang"
    },
    {
      "name": "X. Lei"
    },
    {
      "affs": [
        0
      ],
      "name": "C. Zhang"
    },
    {
      "name": "X. Zhao"
    },
    {
      "name": "Z. Fan"
    },
    {
      "name": "B. Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4jsy6b7et6hwt.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.01.748473",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748473v1.full",
  "id": "4jsy6b7et6hwt",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748473v1",
  "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": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2808|Barrier Structure and Function Studies"
    ]
  ],
  "openalex": "W7208823356",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748473v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4jsy6b7et6hwt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:35Z",
      "native_id": "10.64898/2026.09.01.748473",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.01.748473v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Transthyretin Contributes to Hippocampal Blood-Brain Barrier Recovery Following Intestinal Inflammation, with Reduced Expression in Alzheimer's Disease",
  "title_text": "Transthyretin Contributes to Hippocampal Blood-Brain Barrier Recovery Following Intestinal Inflammation, with Reduced Expression in Alzheimer's Disease",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:35Z",
  "url": "https://research.draconitic.com/paper/4jsy6b7et6hwt",
  "venue": "bioRxiv",
  "versions": []
}