{
  "id": 17204004,
  "title": "Differential endothelial cell remodeling in Down syndrome and APP duplication drives distinct blood brain barrier dysfunction",
  "url": "https://urgent.news/2026/10/30/differential-endothelial-cell-remodeling-in-down-syndrome-and-app",
  "topic": "tech",
  "section": "Tech",
  "published": "2026-10-30T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.29.762815v1?rss=1"
  },
  "original_language": "en",
  "account": "Endothelial cells (ECs) in individuals with Down syndrome (DS) and APP duplication (APPdup) display altered remodeling and distinct blood-brain barrier (BBB) dysfunction, increasing susceptibility to cerebral amyloid angiopathy (CAA). A duplication of the amyloid precursor protein (APP) gene in APPdup leads to heightened AD risk and CAA compared to DS with AD. Researchers examined EC function and BBB integrity in DS and APPdup using human induced pluripotent stem cell-derived ECs (iECs) to discern the impact of multiple chromosome 21 copies.\n\nBoth DS and APPdup iECs increased Aβ40/Aβ42 secretion compared to their isogenic controls, but the profiles diverged. DS iECs exhibited enhanced junctional protein expression and diminished permeability, while APPdup iECs showed heightened permeability. Transcriptomic profiling of DS iECs unveiled extensive dysregulation, amplifying junctional, adhesion, angiogenic, immune, and apoptosis pathways, while suppressing cell-cycle, proliferative, and membrane-targeting signatures. APPdup iECs experienced milder alterations, encompassing impaired protein targeting and reduced adhesion-related pathways.\n\nDespite equivalent APP dosage, DS iECs retained superior junctional integrity and lower permeability than APPdup iECs. This differential resilience may contribute to the disparate CAA vulnerability between DS and APPdup. However, compromised proliferation and altered angiogenesis in APPdup iECs might weaken BBB resilience as individuals age.",
  "summary": "An extra copy of the amyloid precursor protein gene (APP) is present in Down syndrome (DS) and APP duplication (APPdup), increasing the risk of Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA). However, we reported greater vascular A{beta} deposition in APPdup than in DS with AD, suggesting that other triplicated chromosome 21 genes may mitigate CAA severity. We investigated…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}